Neuroplasticity a cikin jaraba: ra'ayoyin salon salula da kuma rubutun (2012)

Front Neurosci. 2012. 5: 99.

An wallafa shi a kan layi na 2012 Nuwamba 12.. doi: 10.3389 / fnmol.2012.00099

PMCID: PMC3495339

Heather B. Madsen,^1,^† Robyn M. Brown,^1,^*^† da kuma Andrew J. Lawrence^1,²

Bayanin marubucin ► Mataki na asali ► Bayanin Copyright da License ►

Ka tafi zuwa ga:

Abstract

Magungunan ƙwayar maganin likita ne mai ci gaba, ta sake kwakwalwa ƙwayar cuta ta kwakwalwa wadda ta ƙunshi dabi'u masu tilasta yin amfani da miyagun ƙwayoyi da kuma daukar abin da ke faruwa a sauran ayyukan. Tsarin mulki daga jima'i zuwa amfani da miyagun ƙwayoyi masu karfi da kuma ciwon dawwama na sake dawowa ana zaton za'a aiwatar da su ta hanyar tsararruwar tsararraki a cikin ƙwararrun ƙwararrun ƙwararru, kamar misalin waɗanda ke da ƙaddamarwar ƙwaƙwalwar ƙwaƙwalwa. Binciken da aka gudanar a cikin shekaru ashirin da suka gabata ya haifar da matukar cigaba a gano hanyoyin tsarin kwayoyin halitta da kwayoyin halitta wanda ke taimakawa wajen canza canjin magani da kuma halayyar kamfanoni..

Canje-canjen a cikin hanyar synaptic a cikin hanyoyin da ake kira mesocorticolimbic da hanyoyin corticostriatal, da canje-canje a cikin yiwuwar rikodin kwayoyin halitta ta hanyar jinsunan halittu su ne mahimman hanyoyi guda biyu wanda magungunan zalunci zai iya haifar da canje-canje a cikin hali.

A cikin wannan bita mun samar da taƙaitaccen binciken da aka yi a baya-bayan nan wanda ya kara fahimtar fahimtar ƙananan kwayoyin halitta wanda ya haifar da matakan cigaba a matakin ɓarna, da kuma yadda za a iya canza waɗannan canji ga cututtukan mutum.

keywords: jaraba, filastik, CREB, deltaFosB, epigenetics, gyara tarihi, DNA methylation, microRNAs

Ka tafi zuwa ga:

Gabatarwa

Addictionarawar ƙwayoyi cuta ce ta yau da kullum, rikicewar rikicewa wanda ke da alaƙa da sarrafawa, amfani da ƙwayoyi masu tilasta amfani da shi wanda ke ci gaba duk da mummunan sakamako. Aya daga cikin mafi girman sifofin jaraba shine mai saurin jurewa don sake dawowa da masu amfani suka nuna duk da watanni ko ma shekarun kamewa (O'Brien, 1997). Abin mahimmanci, ba kowa da ke amfani da kwayoyi ya zama kamu, kuma ko mutum ya sa wannan canji zai iya rinjayar shi ta hanyar rikitarwa na kwayoyin halittu da kuma muhalli (Goldman et al., 2005; Kendler et al., 2007). Ƙara yawan yin amfani da miyagun ƙwayoyi daga jarabawa zuwa gajiya da damuwa na cigaba da sake dawowa anyi zaton zai zama jagorancin kwakwalwa na tsawon lokaci a cikin kwakwalwa ta hanyar ladabi (Thomas et al., 2008; Luscher da Malenka, 2011; Robison da Nestler, 2011). EDuk da haka dukkanin magungunan ƙwayoyi suna yin amfani da kayan haɓaka mai karfi ta hanyar hanyar damun kwayoyi na mesocorticolimbic, sun hada da kwayoyin dopamine wanda ke samuwa a cikin yanki na kwakwalwa (VTA) da kuma aikin zuwa ga striatum da sauran yankunan limbic wanda ya hada da kodayake na farko (PFC), amygdala da hippocampus (Di Chiara da Imperato, 1988; Le Moal da Simon, 1991).

Har ila yau, striatum yana karɓar rubutun almara daga PFC, kuma yayin da mesolimbic dopamine bai zama mahimmanci ga matakai na farko na shan magani da kuma ƙarfafawa ba, wani muhimmin tasiri ga fassarar glutamate corticostriat a cikin yanayin da ke da karfi da kuma jurewa yana ƙara fahimta (Kalivas, 2009; Kalivas et al., 2009). Babban mayar da hankali kan bincike a halin yanzu shine ke nuna fasalin kwayoyin halitta da kwayoyin da ke faruwa a cikin wannan motsi na motsa jiki don taimakawa wajen bunkasa ci gaba da jurewa. A cikin dakin gwaje-gwaje, ana iya bincika abubuwa daban-daban na jarabawa ta hanyar amfani da dabba (taƙaitacce a cikin Table Table1).1). Dalilin wannan bita shine samar da wani bayyani game da canje-canjen neuroplastic da ke faruwa a synapse, kuma a kan matakin rubutu na gizon, wanda ke taimakawa wajen halayyar halayen haɗari.

Table 1

Ƙwaƙwalwar bidiyo a cikin dabbobi.

Amfani da Locomotor: Bayanin Locomotor ya kwatanta cigaba na cigaba a aikin locomotor wanda ya saba da maimaitawa, yaduwar miyagun ƙwayoyi. Sensitization zai iya jure wa watanni ko ma shekaru bayan janyewa, kuma saboda haka an ɗauka shine alamar jigilar ƙwayar magani (Steketee, 2003). Kodayake yawancin binciken da aka shafi game da psychostimulants, an gano mahimmanci akan amsawa ga masu amfani da opiates, nicotine da ethanol (Shuster et al., 1977; Kalivas da Duffy, 1987; Robinson et al., 1988; Benwell da Balfour, 1992; Cunningham da Noble, 1992). An nuna alamar fahimtar juna tsakanin magunguna daban-daban na zalunci, yana nuna cewa hanyoyin da aka saba amfani da su sune ci gaba da wannan abu duk da irin wadannan kwayoyi da ke da kwakwalwa a cikin kwakwalwa (Vezina da Stewart, 1990; Itzhak da Martin, 1999; Beyer et al., 2001; Cadoni et al., 2001).

Yanayi da aka zaɓa (CPP): CPP wani nau'i ne mai mahimmanci na sakamako na miyagun ƙwayoyi bisa ka'idodin ka'idodin gargajiya (Pavlovian) (Tzschentke, 1998). Kwamfutar CPP tana kunshe da yanayi daban-daban guda biyu, ɗaya daga cikin abin da aka haɗa tare da miyagun ƙwayoyi, kuma tare da maimaita yanayin da aka haɗa da miyagun ƙwayoyi yana samun kyawawan kayan haɓaka na sakandare waɗanda zasu iya haifar da halayyar haɗin kai. An ce an sami dabba a matsayin zaɓi idan ya ciyar da lokaci mafi yawa a yanayin da aka haɗa da miyagun ƙwayoyi lokacin da aka ba da zabi. Ana amfani da wannan tsari don auna ladaran likitanci da ƙwarewa.

Gwamnatin kai-tsaye:Ana iya horar da dabbobi don gudanar da sha'anin kansu mafi yawancin kwayoyi da mutane suke amfani dashi. Ana amfani da wannan ta hanyar amfani da akwatunan sarrafawa inda aikin injiniya kamar lakabi mai mahimmanci ko hanci kamuwa da sakamakon ƙwayar magani ko ladabi. Za a iya ba da kyauta kyauta tare da wani abu mai mahimmanci irin su sautin ko hasken, ko kuma abubuwan da ke faruwa a cikin mahallin.

Ƙarshe / sakewa: Hanyoyi yana nuna raguwa a yanayin halayen miyagun kwayoyi bayan an sake ƙarfafa shi (Myers da Davis, 2002). Za a iya yin haɓaka a cikin mahallin CPP, inda aka nuna dabba da yawa a yanayin da aka haɗa da miyagun ƙwayoyi idan babu magani. Da zarar an kashe CPP, za'a iya sake shigar da shi ta hanyar yin amfani da kwayoyi (Mueller da Stewart, 2000) ko yin tasiri ga masu ƙarfafawa (Sanchez da Sorg, 2001; Wang et al., 2006). Za a iya shafe halayyar kai tsaye ta hanyar kawar da maganin miyagun ƙwayoyi, sa'an nan kuma a sake dawo da su daga magungunan miyagun ƙwayoyi (Dewit da Stewart, 1981), ɗaukar hotuna zuwa alamun ko alaƙa da suka haɗa da miyagun ƙwayoyi (Meil da Duba, 1996; Weiss et al., 2000; Crombag da Shaham, 2002), ko ɗaukar hotuna ga danniya (Shaham da Stewart, 1995; Erb et al., 1996; Shepard et al., 2004). Wadannan abubuwan sune sanadiyar motsa jiki da kuma sake dawowa cikin jarabar mutum, da kuma irin wannan yunkuri na sake dawowa a cikin dabbobi.

Ƙwaƙwalwar bidiyo a cikin dabbobi.

Ka tafi zuwa ga:

Hanyoyi masu amfani da launi na synaptic: jaraba a matsayin tsari na ilmantarwa da ƙwaƙwalwar ajiya

Binciken cewa daukar shan magani da kuma sake dawowa suna da alaka da sauƙin kai tsaye ga shafukan likitoci da ke nuna muhimmancin ayyukan ilmantarwa na tarayya a cikin buri (Wikler da Pescor, 1967; Tiffany da Drobes, 1990; O'Brien et al., 1998). Steven Hyman ya nuna cewa "rikitaccen ƙwaƙwalwar ajiya ana ɗauka a matsayin yanayi wanda ya haddasa asarar ƙwaƙwalwar ajiya, amma idan kwakwalwa ya tuna da yawa ko kuma ya yi rikodin ƙungiyoyi masu zaman kansu?" (Hyman, 2005). A cikin wannan mahallin, buri za a iya ganewa, a kalla a wani ɓangare, a matsayin tsari na ilmantarwa da ƙwaƙwalwar ajiya. A cikin goyan bayan wannan binciken da aka yi a cikin shekaru goma da suka gabata, ya nuna cewa maganin zalunci ya yi gyaran gyare-gyaren synaptic a cikin mesocorticolimbic da corticostriatal circuitry ta hanyar irin wannan tsarin da ke haifar da ƙaddamarwar ƙwaƙwalwar ajiyar lokaci. Abin da waɗannan gyare-gyare suke wakiltar ainihin halin hali da jaraba gaba ɗaya shine wani, watakila ƙalubale, tambaya. Sashe na gaba zai duba abubuwan da aka saba amfani da shi na maganin da ake amfani da shi don magance ƙwayoyin cuta kamar yadda ake auna electrophysiologically a cikin yanayin dabba da kuma muhimmancin su ga yanayin da aka kamu.

Santiago Ramon y Cajal ne wanda, a kan 100 shekaru da suka wuce, yayi la'akari da ra'ayin cewa canzawa cikin ƙarfin haɗin synaptic dake tsakanin mahaukaci zai iya zama hanyar da kwakwalwa ta kera bayani (Cajal, 1894). Binciken da ake samu na tsawon lokaci (LTP) a cikin hippocampus a cikin 1973 ya ba da shaida ta farko cewa wannan zai iya kasancewa (Bliss da Lomo, 1973). LTP ne ingantaccen ƙarfin haɗin synaptic wanda ya haifar da firgitawa na haɗuwa da igiyoyi, yayin da takwaransa na tsawon lokaci (LTD) shine raunana ƙarfin synaptic (Citri da Malenka, 2008). Wadannan matakai sukan haɗa da raunin masu karɓa na N-methyl-D-aspartate (NMDA) na mai-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) zuwa kuma daga tantanin halitta (Kauer da Malenka, 2007). Ana haɓaka ƙimar mai karɓa na NMDA a matakan calcium a cikin cell postsynaptic don buƙatar LTP da LTD, tare da adadin alakar da ke ƙayyade jerin abubuwans. Ƙara yawan ƙaruwa a cikin ƙwayoyin zazzafar kunna haɓakar haɓakar ƙwayar cuta kuma ya haifar da LTP, an bayyana shi a matsayin ingantaccen watsawa a masu karɓa na AMPA postsynaptic.

Sabanin haka, karin sauƙi a cikin ƙwayoyin calcium zai kunshi sunadarai phosphatases da kuma samar da LTD, wanda aka bayyana a matsayin ragu a watsawar mai karɓar AMPA (Kauer da Malenka, 2007). WLTP da LTD sun fara binciken game da ilmantarwa da kuma ƙwaƙwalwar ajiya a cikin hippocampus, yanzu an san su suna faruwa a mafi yawan hanyoyin synapses a cikin tsarin tsakiya na tsakiya, kuma suna da mahimmanci ga nau'o'in nau'i na nau'in kwarewa mai zurfi. (Malenka da Bear, 2004; Kauer da Malenka, 2007).

Drug-evoked potentiation a excitatory synapses a cikin VTA

Nazarin farko da Ungless da abokan aiki suka yi a 2001 ya nuna cewa sau ɗaya da ake nunawa zuwa cocaine ya haifar da ingantaccen ƙarfin synaptic a raguwa ta hanyar VTA DA neurons lokacin da aka auna 24 a baya a cikin kwakwalwa ta jiki (Ungless et al., 2001). An kiyasta wannan a matsayin haɓaka a cikin raƙuman bayanan mai kwakwalwa (EPSC) wanda aka sanya wa jarrabawa a kan ƙananan EPSC (wanda ake kira AMPA / NMDA). An gabatar da LTP na lantarki wanda aka ba da wutar lantarki ta hanyar yin amfani da shi ta hanyar lantarki ta hanyar haɗin gwiwar VTA synapses. Wadannan bayanai da kuma sauran matakan lantarki sun nuna cewa canji a cikin filastik ya lura da yiwuwar rabawa irin wannan hanyar zuwa LTP da aka saba da shi (Ungless et al., 2001). An nuna cewa gwamnati na sauran magungunan magungunan ciki har da amphetamine, morphine, ethanol, nicotine, da benzodiazepines na iya haifar da karuwa a ƙarfin synaptic a cikin VTA, wani sakamako da ba a gani tare da kwayoyi masu kwakwalwa da ba su da wata mummunar haɓaka (Saal et al., 2003; Gao et al., 2010; Tan et al., 2010). Wannan kallo yana nuna rikitarwa na sakonnin salula a cikin VTA ta duk kwayoyi da ake amfani da su kuma ya samar da wata hanyar da za ta iya yiwuwa ta hanyar da za'a iya haifar da jarabawar ƙwaƙwalwa.

Sakamakon rikon kwarya na miyagun ƙwayoyi a kan Vista synaptic filastity an nuna shi a hankali, wanda zai iya kasancewa aƙalla 5 amma kasa da kwanaki 10 kuma an nuna ya dace da haɓakawa na haɓaka halayyar hali amma ba tare da furtawa ba (Ba da kuma al., 2001; Saal et al., 2003; Borgland et al., 2004). Idan an yi amfani da cocaine kai tsaye, sakamakon ya bambanta kamar yadda filastik a cikin VTA ya kasance mai ci gaba kuma ana iya gano ko da 90 kwanakin zuwa janyewa (Chen et al., 2008).

A potentiation na glutamatergic synapses a kan VTA DA sel ne mai yiwuwa yiwuwa ya danganta da ikon da kwayoyi na zagi don inganta extracellular DA a cikin NAc (Di Chiara da Imperato, 1988) da kumaWadannan suna wakiltar farawa na ilimin ilimin "pathological" wanda ya haifar da "ƙwaƙwalwa" a cikin ƙungiyoyin magunguna. Babu shakka, yawan ƙarfin mai karɓar mai karɓa na NMDA na ƙaruwa a cikin VTA DA neurons a lokacin sayen wata ƙungiya mai suna (Stuber et al., 2008) kuma kwanan nan an tabbatar da cewa cocaine yana ƙara ƙarar AMPA / NMDA na wajan VTA wanda ke aiki zuwa NAC kamar yadda ya saba da PFC (Lammel et al., 2011); an tabbatar da cewa kwayar cutar kwayar cutar ta DNA a cikin NAC na da muhimmanci ga sayen ƙungiyar Pavlovian (Kelley, 2004). Saboda haka yana iya kasancewar cewa VTA DA neurons zai iya wakiltar ƙwayoyin ƙididdigar su kamar LTP, yiwuwar tsarin koyarwa, wanda yana da mahimmanci don maganganun halayyar halayyar hawan cocaine wanda ya haifar da damar da za a faɗakar da sababbin lokuttan da suka haifar da buri, ko da yake ba ya wakilci halin da ya kamu da kansa ba. Kamar yadda wasu suka bayar, watakila magungunan ƙwayoyi suna taimaka wa ƙwaƙwalwar ƙwaƙwalwar ƙwaƙwalwar ƙwaƙwalwa don "overlearn" darajar miyagun ƙwayoyi ga kwayoyin halitta (Kauer da Malenka, 2007).

Asali daga mahimman abubuwan da aka yi amfani da shi ga VTA da ke cikin magungunan miyagun ƙwayoyi suna kasancewa a cikakke. Ɗaya daga cikin binciken ya bayyana cewa VTA glutamatergic synapses da aka yi niyya daga duka VTA da kanta da kuma pedunculopontine nucleus (PPN) ya nuna inganta haɓakarwa daga cocaine duk da haka kawai synapses samun labari daga PPN masu shafewa suna da haɗari tare da Δ⁹-tetrahydrocannabinol (THC) (Good da Lupica, 2010). Saboda haka, yana nuna cewa magunguna masu amfani da kwayar cutar da ke tattare da miyagun ƙwayoyi na iya bambanta bisa ga miyagun ƙwayoyi da ake tambaya kuma yana iya kasancewa cewa akwai wani tsari na musamman ga dukkanin ƙwayar ƙwayar cuta ta VTA; Har yanzu ba a yanke shawara ba. Tya VTA ya sami matakai masu yawa daga sassa daban-daban na kwakwalwa ciki har da PFC, amygdala da kuma subthalamic nucleus (Geisler and Wise, 2008), da yawa daga cikinsu an nuna su tasiri da fashe firing daga VTA DA neurons (Grillner da Mercuri, 2002). Gwaje-gwaje na gaba da amfani da fasahar optogenetic zasu iya taimakawa wajen tantance maƙasudin musamman da ke da alhakin maganin ƙwayar cuta a VTA synapses wanda aka lura da shi don maganin magunguna daban-daban na cin zarafi, saboda haka zubar da haske akan ainihin yanayin wannan neuroadaptation.

Hanyoyin da ke tattare da maganin ƙwayar cuta ta hanyar maganin ƙwayar cuta ne a VTA

Kamar dai tare da LTP a cikin kwakwalwa a cikin tsakiya da DA neurons an ƙaruwa yawan ƙarfin synaptic a cikin VTA da aka haifa ta hanyar cocaine da nicotine. dogara ne akan kunnawa mai karɓa na NMDA (Bonci da Malenka, 1999; Babu kuma al., 2001; Mao et al., 2011). Sabanin haka, an tabbatar da tabbatar da halayyar halayyar hawan cocaine a cikin kwanan nan da ake bukata na aikin gina jiki kin Masi (Ho et al., 2012), haɓakar ƙarancin kinosin CINA (PKC) mai cin gashin kanta, yayin da LTP dogara a cikin lokaci a cikin VTA da ƙananan ƙwayoyin magungunan ƙwayoyi masu guba na dogara ne akan kamfanonin PKC na al'ada (Luu da Malenka, 2008). A yanayin sauƙin nicotine VNA na da yiwuwar haɓakawa ta hanyar haɓakar DA neurons wanda aka ba da damar yin amfani da su ta hanyar α4β2 nicotinic acetylcholine receptors (nAChRs) (Mao et al., 2011). Ƙasar Nicotine ƙaddamar da ƙaddamar da suturar glutamate suma kuma yana taimakawa wajen shigar da wannan nau'in haɗin gizon synaptic, mai yiwuwa ta hanyar ƙaruwa daga masu karɓa na NMDA (Mao et al., 2011).

Ana danganta karin bayani game da hanyoyin da ake amfani da su na synaptic wanda ke haifar da hawan cocaine fiye da yadda wasu kwayoyi masu cin zarafi suka haifar. Yin amfani da Cocaine zuwa tsakiya na tsakiya yana haifar da yiwuwar watsawa na NMDA a cikin minti kaɗan kuma an ba da shawara ta kasance ta hanyar saka NR2B-dauke da NMDARs zuwa synapses ta hanyar hanyar da ake buƙatar kunnawa D₅ masu karɓa da sababbin sunadarin sunadaran (Schilstrom et al., 2006; Argilli et al., 2008). An kuma nuna alamar Aikin Orexin A da ake bukata don shigar da hakin NR2B mai dauke da hankalin cocaine tare da kara yawan AMPA / NMDA; bisa ga ƙaho₁ Sakamakon mai amfani da SB334867 mai karɓa ya nuna cewa ya hana a cigaba da cigaba da haɓaka ga cocaine (Borgland et al., 2006). Bugu da ƙari, canje-canje a cikin maganin mai karɓa na NMDA, ƙananan matakan GluR1-dauke da (GluR2-rasa) masu karɓar AMPA a synapses an kiyaye su da zarar 3 h bayan halayyar cocainee (Argilli et al., 2008). Wannan kallon da aka hade tare da wasu shaidu na baya-bayan nan ya haifar da tsammanin cewa sakawa masu karɓar GluR2 mai kula da hakar gwaninta suna taimakawa wajen nuna halayen synaptic mai kwakwalwa a cikin VTA (Dong et al., 2004; Bellone da Luscher, 2006; Mameli et al., 2007; Brown et al., 2010; Mameli et al., 2011), don dubawa (Kauer da Malenka, 2007; Wolf da Tseng, 2012). Wannan shigarwa na GluR2-rashin masu karɓar raƙuman AMPA ya dogara da watsawar mai karɓa na NMDA a VTA DA neurons tun lokacin da ba shi da shi a cikin ƙananan yara ba tare da aikin NMDA masu karɓa a DA neurons (Engblom et al., 2008; Mameli et al., 2009). NiNassar GluR2-rasa masu karɓa na AMPA yana da muhimmanci saboda suna da kaya masu yawa; sune sunadaran sunadaran, suna da halayyar tashar tashar sadarwa fiye da GluR2-dauke da masu karɓa, sabili da haka suna da babbar damar canza canjin synaptic (Isaac et al., 2007). Saboda haka, saka GluR2-rashin masu karɓa na AMPA a cikin VTA na wakiltar wata hanyar da za ta iya amfani da ita don yin amfani da magungunan ƙwayoyi na iya haifar da gyaran ƙwayar filastik wanda ya haifar da matakin farko na yin amfani da miyagun ƙwayoyi.

An saka GluR2-rasa masu karɓa na AMPA a cikin VTA excitatory synapses a halin da ake ciki don mayar da martani ga kula da magungunan kwayoyi daga nau'o'i da yawa kamar nicotine da morphine da kuma a kan kunnawa optogenetic na DA VTA neurons (Brown et al., 2010). Tshi ya jagoranci shawara cewa sakawa da kwaminis-gwargwadon GluR2-rashin masu amfani da AMPA sun wakilci duniya na inji wanda zai iya haifar da miyagun ƙwayoyi-evoked potentiation na VTA synapses (Brown et al., 2010), kodayake bayanan amphetamine ba daidai ba ne da wannan batu (Faleiro et al., 2004). Bugu da ƙari, kamar yadda GluR2-rasa masu karɓa na AMPA suna yin gyare-gyare a ciki kuma don haka ba su da yawa a halin yanzu a + 40 mV, ƙaddamar da su kadai ba zai iya bayyana ƙananan haɓakar likitanci a lissafin AMPA / NMDA ba. Wani binciken da aka yi a kwanan nan wanda yayi la'akari da amsoshin maganganu guda ɗaya wanda aka samo shi ta hanyar mafita mai mahimmanci (photolysis guda biyu). al., 2011), don haka samar da wata hanyar da za ta iya amfani da lissafin AMPA / NMDA a cikin wannan labari (ta hanyar rage yawan ƙididdigar rabo). Wannan har yanzu ba a bincika tare da wasu magunguna ba.

Canjin da aka yi amfani da miyagun ƙwayoyi na GluR2-dauke da GluR2-rasa masu karɓa na AMPA za a iya juyawa ta hanyar kunna masu karɓa na mGluR1 a VTA (Bellone da Luscher, 2006; Mameli et al., 2007). Sabili da haka, musayar mGluR1 na jarrabawa na AMPA na samar da wata hanyar da za ta iya bayyana dalilin da yasa maganin cutar VTA ya kasance mai saurin yanayi, 5 mai zaman kanta amma ba 10 kwanakin (Ungless et al., 2001; Mameli et al., 2007). Lalle ne, idan mGluR1 aiki a cikin VTA ya rage 24 h kafin cocaine mulki to, cocaine-induced inward rectification ya ci gaba fiye da 7 days (Mameli et al., 2007, 2009). Saboda haka wata hujja ta yiwu akan dalilin da yasa cigaban haɗin gwiwar hawan cocaine ya ci gaba a cikin VTA bayan sha'anin gwanin cocaine (ba kamar bin tsarin da ba ta da ma'ana ba) zai iya zama cewa tsarin kai na cocaine zai kai ga bakin ciki na mGluR1 a cikin VTA.

Hanyoyin maganin synaptic kwayar cutar ta hanyar ƙwayar cuta a cikin ƙwayar maganin synapses a cikin VTA

Exnitatary synapses ba kawai ne kawai nau'in synapse a cikin VTA DA neurons wanda aka shafi da ba contingent gwamnatin da kwayoyi na zagi. Rikicin synapses a cikin VTA yana da muhimmiyar rawa a sarrafa iko da kamfanonin DA neurons, saboda haka ladaran a GABAergic synapses yana da ikon iya rinjayar tasiri DA watsawa. Hakika, cocaine, morphine da ethanol zasu iya rinjayar ladabi na synaptic a cikin VTA (Melis et al., 2002; Liu et al., 2005; Nugent et al., 2007). Maganin cocaine mai maimaitawa a vivo don kwanakin 5-7 yana haifar da raguwa a cikin amplitudes na hanyoyin synaptic da aka ƙaddamar da GABA, ta hanyar samar da shigarwa na LTP cikin sassan VTA ta rage ƙarfin GABAergic na hanawa (Liu et al., 2005). Nazarin na ƙarshe ya nuna ma'anar wannan ƙin ya zama EndDannabinoid-dogara LTD a GABAergic synapses ciki har da kunnawa na ERK1 / 2 (Pan et al., 2008, 2011). GABA_A mai karɓa synapses a kan VTA dopamine neurons kuma nuna karfi NMDA-dogara LTP (ya kira LTP_Gaba) a mayar da martani ga ƙarfin hawan mita (Nugent et al., 2007). Wannan LTP_Gaba ba shi da shi a cikin VTA jerin 2 da / ko 24 h bayan a vivo gwamnatin morphine, nicotine, cocaine ko ethanol (Nugent et al., 2007; Guan da Ye, 2010; Niehaus et al., 2010). A yanayin saukan ethanol rigakafin LTP_Gaba an saka shi ta hanyar mai karɓar μ-opioid (Guan da Ye, 2010) Tare da haɗin gwiwar synaptic a fyaucewa na hargitsi, wannan asarar LTP_Gaba ya kamata kara yawan kamfanonin VTA DA neurons da ke biyewa da miyagun ƙwayoyi.

Slow GABA transmission an nuna kwanan nan da za a shafa da kwayoyi na zagi. Ta haka ne kashi guda na methamphetamine ko cocaine ya isa ya zama mai raunana ikon GABA_B masu karɓa don sarrafa VTA GABA neuron firing lokacin da aka auna ex vivo 24 a baya (Padgett et al., 2012). Rashin ƙaddamar da ƙwayar methamphetamine na jinkirta jinkirin mikiya na postsynaptic (IPSC) ya fito ne daga raguwa a GABA_B gwargwadon ƙwayar haɗin gizon-G wanda aka haɗu da haɗin gwanin-mai-g-g a cikin ciki, saboda canje-canje a fataucin furotin, kuma yana tare da raguwar karuwa a hankali na GABA mai mahimmanci._B masu karɓa a GABA neurons na VTA. Ba kamar magungunan miyagun kwayoyi ba a GABA_A Gyaran wannan matsalar ta GABA_BR-GIRK sigina na cigaba da na tsawon kwanaki bayan injection (Padgett et al., 2012).

Abubuwan da ke tattare da miyagun ƙwayoyin cuta-evoked potentiation a cikin VTA DA sassan

Kamar yadda aka ambata a baya, sakamakon tasirin miyagun ƙwayoyi marasa amfani a kan maganin synaptic a cikin VTA DA neurons an nuna shi a hankali, yana da maƙalla aƙalla 5 amma kasa da 10 kwanakin kuma an nuna shi ya dace da haɓakawa na haɓaka halayyar hali amma ba tare da furtawa ba (Ba da kuma al., 2001; Saal et al., 2003; Borgland et al., 2004). Don tallafawa ra'ayin cewa maganin maganin VTA synapses yana wakiltar haɓakar haɓakar halayyar halayen, haɗin gwargwadon VTA na masu tsauraran ƙwayoyi na glutamate sun rage, kuma tsarin GluR1 da aka tsara a hanzari ya kara inganta halayen masu amfani da kwayoyin locomotor (Carlezon et al., 1997; Carlezon da Nestler, 2002). Tabbas mai karfi na NR2A- da B da ke dauke da NMDA mai karɓar mai karɓa suna samuwa ta hanyar lura cewa dakatarwar pharmacological na ko dai ya hana duka ci gaba da mahimmanci da haɗin haɗin hawan cocaine haɓaka cikin halayen AMPA / NMDA (Schumann et al., 2009). Duk da haka, mice tare da maye gurbin NR1 ko GluR1 (zaɓi zuwa tsakiyarbrain DA neurons) ko kuma sharewar GluR1 a duniya yana nuna halayyar dabi'a marar kyau kuma duk da haka ya nuna tasirin mai karfin AMPA marasa lafiya bayan maganin cocaine (Dong et al., 2004; Engblom et al., 2008). Ƙarar daɗaɗa ta kunshe ne ta hanyar lura cewa CPP da yanayin haɗin locomotor yanayin ba shi da shi a cikin GluR1 knockout mice (Dong et al., 2004) da kuma lalacewar cocaine CPP ba shi da shi a cikin ƙananan yara tare da maye gurbin GluR1 wanda ake nufi da tsakiyarbrain DA neurons (Engblom et al., 2008), alhãli kuwa a cikin NR1 knockout mice reinstatement na cocaine CPP da kuma bayyana halin haɓaka hali ne an attenuated (Engblom et al., 2008; Zweifel et al., 2008). Sabili da haka, koda yake tare da cajin da za'a iya samu na ci gaba a cikin ƙwayoyin mikiya da / ko yiwuwar cirewa ba tare da cikakke ba, zai yiwu cewa tsarin tafiyar da hanyoyin da ake sarrafa magungunan DA neurons da halayen halayen hali ba su da katsewa. Maimakon haka yana iya kasancewa cewa cin hanci da rashawa na VTA zai iya taimakawa wajen ba da jituwa ga jigilar magunguna.

Gyaran canje-canje na synaptic da ke biye da gwamnatin miyagun ƙwayoyi marasa dacewa an iyakance ne game da sanar da ainihin yanayin rashin illa. Mafi dacewa da yanayin mutum shine nazarin inda za'a canza canje-canjen synaptic ta hanyar bin magungunan miyagun ƙwayoyi kamar yadda ake gudanarwa. A wannan bangare, ƙarfafa synaptic na VTA DA sassan da aka samu ta hanyar mulkin kai na cocaine yana da mahimmanci, watau watanni 3 mai dorewa cikin abstinence kuma an nuna su zama masu tsayayya ga horarwa (Chen et al., 2008). Saboda haka, ko da yake an fara gabatar da shi a matsayin wani abu mai rikitarwa, yana nuna cewa ƙwayar magungunan ƙwayoyi a cikin VTA yana da damar da za ta kasance mai dorewa, yana nuna cewa hanya na gwamnati (wanda ya haɗa da wanda ba shi da ma'ana) yana da mahimmancin ƙaddarar tsawon rayuwarsa. . Wannan yana taimakawa ta hanyar lura cewa hada-hadar haɗe-haɗe a wannan binciken bai nuna irin wannan karuwa ba a cikin tsarin AMPA / NMDA; yana cewa yana da ilmantarwa akan ladabi ko ƙungiyoyi masu aiki da ke motsawa. Sabanin haka, aikin kai na abinci ko sucrose a karkashin sifofin irin wannan ya haifar da halayen AMPA / NMDA wanda ya ci gaba da 7 amma ba 21 kwanakin zuwa abstinence ba, wanda ya nuna rashin daidaito idan aka kwatanta da abin da cocaine ya haifar (Chen et al., 2008). Rashin ci gaba da yin amfani da abincin da aka haifar da abinci ya nuna cewa canji a cikin ƙarfin synaptic da cocaine ya haifar ba kawai wani nau'i ne na aikin koyarwar kayan aiki ba ko ƙwarewa wanda ke cikin tsarin tsarin mulkin kai da se, maimakon magungunan miyagun ƙwayoyi wanda zai iya wakiltar ƙaƙƙarfan maganin ƙwayar magungunan ƙwayoyi. Kamar yadda aka ambata a baya, an gano alamomin sakamako don haifar da haɓakar AMPA / NMDA a cikin VTA, kodayake ba a matsayin mai ci gaba ba, goyon baya ga rawar da za a yi don gyaran aikin synaptic a cikin sakamako na illa (Stuber et al., 2008).

Abin sha'awa, girman girman karuwar AMPA / NMDA shi ne irin wannan ba tare da la'akari da adadin injections (guda da nau'i ba), Yarjejeniya ta gwamnati (maƙasudin ci gaba da wanda ba ya gudana), da kuma tsawon lokacin samun dama (iyaka da dama don samun dama) (Borgland et al., 2004; Chen et al., 2008; Mameli et al., 2009). Wannan yana nuna cewa karuwa a tsarin AMPA / NMDA da aka lura a cikin VTA DA sassan yana yiwuwar haɓakaccen ƙullin, watakila alama "salience" a matsayin tsayayya da wakiltar ƙaddamar da ƙwararrun kwayoyin halitta wanda zai yiwu ya ƙara yawan ci gaba.

Hanyoyin da ke dauke da kwayar cutar a cikin NAc

Ba kamar VTA ba ne kawai a cikin allurar cocaine ba zai haifar da ƙara yawan ƙarfin synaptic a NAC ba lokacin da aka auna 24 a baya (Thomas et al., 2001; Kourrich et al., 2007). Wannan kallo da kuma lokuta na biyun da suka biyo baya tare da gwamnati tare da janye dya tabbatar da cewa ƙwayar cuta da aka haifar da miyagun ƙwayoyi a cikin NAc alama ce ta bambanta da abin da aka lura a cikin VTA. Lalle ne, yayin da ake yin maganin ingancin cocaine (don haɓaka halayyar halayyar halayya), haɓaka a cikin tsarin AMPA / NMDA ana lura a kan synapses na NAc lokacin da aka auna 24 h bayan bayanan karshen (Kourrich et al., 2007). Wannan cututtukan synaptic daga cocaine mai maimaita ya nuna cewa an danganta shi da filastik a cikin VTA; a kan zazzagewar zaɓi na aikin mGluR1 a cikin VTA kawai kawai allurar cocaine ne ake buƙatar haifar da wannan baƙin ciki na NAc synapses (Mamel et al., 2009). Tshi mawallafa na wannan nazarin ya yi bayani cewa ingantacciyar motsa jiki na VTA yunkuri na iya sauƙaƙe da saki DA da glutamate a cikin NAc ta hanyar ingantaccen sako na DA. Wannan zai iya canja wurin ƙofar don shigar da filastan gida a cikin NAc ta hanyar tasiri na kewaye ko kuma ta haɗuwa da tsarin sigina na intracellular (Mameli et al., 2009).

Muhimmancin aikin da bakin ciki na NAc ke yi a lokacin karɓa mai zurfi ba shi da kyau a wannan mataki. Wata bayani mai yiwuwa zai kasance cewa damuwa na NAC masu amfani da ƙananan ƙwayoyin cuta (MSNs) sun rage mayar da martani ga abubuwan da suka haifar, saboda haka ya ba da gudummawa ga anhedonia lokacin da aka janye shi. Zai iya kasancewa cewa rage da aka yi a cikin tsarin AMPA / NMDA zai iya haifar da shigar da membrane na NR2B-dauke da masu karɓa na NMDA (saboda haka haɓaka ƙididdigar rabo) yayin da aka gano synapses sauti na farko a cikin harsashin NAC akan halayyar cocaine (Huang et al., 2009). Abubuwan da suka dace da suturar ruwan sanyi, wanda ke nuna nauyin sarrafa nauyin mai karɓa na NMDA ba tare da isassun tashoshi masu karɓa na AMPA ba, ana zaton zasu mallaki ƙarfin ƙarfin ƙarfafa ƙarfin maganin synaptic (Isaac et al., 1995). Da zarar an samar da shi, waɗannan maganganun sauti na iya taimakawa wajen daukar ma'aikatan AMPA ta hanyar inganta haɗin synaptic. Wannan yana samar da wata hanyar da za ta yiwu don bayyana ƙãra a cikin matakin masu karɓar AMPA da kuma AMPAR / NMDAR na gaba wanda aka lura a cikin NAc lokacin da aka janye daga baya (Boudreau da Wolf, 2005; Boudreau et al., 2007; Kourrich et al., 2007; Conrad et al., 2008). NR2B-dauke da masu karɓa na NMDA a cikin NAc na iya shiga tsakani wajen kafa ƙungiyoyi masu magungunan miyagun ƙwayoyi kamar yadda siRNA knockdown na wannan subunit ya hana morpine CPP a cikin ƙananan amma ba haɓaka hali ba (Kao et al., 2011).

Ba kamar cocaine ba, tsarin da aka yi maimaitawar tasirin yaduwar yaduwar yadawa na éthanol a cikin yiwuwar maganin synapses don amsawa ga yarjejeniyar da aka ƙaddara ta LTD-inducing a baya lokacin da aka auna 24 h bayan bayanan karshe (Jeanes et al., 2011). Wannan haɗarin NMDA-dogara ne na gaba kamar yadda bayan 48 h na janyewa ya rushe kuma ba LTP ko LTD za a iya jawo (Jeanes et al., 2011). Mawallafa suna fassara irin wannan canje-canje mai karfi a cikin gurbatacciyar NAC wanda ya nuna mahimmancin muhimmancin wannan tsari a cikin neuroadaptations-induced nehanol. Bugu da ƙari, sabanin magunguna, ethanol zai iya aiki a masu karɓa na NMDA don haka yana da damar yin tasiri mai tasiri na kamfani glutamatergic.

Harkokin haɗin na Synaptic kiyaye a cikin NAc bayan lokacin janyewa

Ya bambanta da raunin da aka gani a yayin da aka janye jiki, an yi amfani da maganin synapses na NAC a bayan kwanaki 10-14 na janyewa daga cocaine maimaitawa ko tsarin morphine (Kourrich et al., 2007; Wu et al., 2012). Bugu da ƙari, bayan 7 kwanakin janyewa daga wata gwamnati ta cocaine, haɓakawa a cikin amplitude na mEPSC da kuma asarar LTP da aka samu ta hanyar hawan mita (HFS) yana samuwa a cikin tsakiya da harsashi NAc neurons suna bayyana dopamine D₁ mai karɓa (Pascoli et al., 2012). Tya canzawa a cikin ikon haifar da filastan synaptic ake kira metaplasticity. Ana kuma lura da maganin maganin maganin cocaine bayan an cire shi daga ginin kansa. Saboda haka, berayen da suke gudanar da maganin cocaine wanda 3 ya biyo baya ko dai bacewa ko abstinence ya nuna alama a vivo kasawa a cikin ikon iya samar da LTP a cikin NAc bayan da ya karfafa PFC. An lura da wannan kallon tare da sauyawa a hagu a cikin shigarwa-fitarwa da ke nuna yiwuwar fEPSP amplitude (Moussawi et al., 2009). Ana iya lura da yiwuwar maganin NAC ta hanyar karuwa ta hanyar AMPA wanda ya biyo bayan wani lokaci mai tsawo bayan abubuwar bayan mulkin kai (Conrad et al., 2008). Gaba ɗaya, waɗannan bayanan sun nuna cewa yiwuwar synaptic a cikin NAC yana tasowa ne a matsayin aiki na tsawon lokacin janyewa, ko a matsayin aiki na tun lokacin da aka fara gudanar da cocaine. Wani bincike na kwanan nan yana goyan bayan fassarar fassarori kamar yadda yakamata a kara yawan ƙwayoyin mEPSC a D₁ mai karɓa-bayyana MSN a cikin ƙuruciya duk da rashi ko kasancewar lokacin janyewar lokaci bayan gwanin cocaine mai sau da yawa (Dobi et al., 2011). Saboda haka, ga alama abubuwan da suka haifar da canje-canje a cikin fassarar glutamatergic a cikin NAc suna ɗaukar lokaci don ci gaba.

Taimakawar takardar shaidar AMPA ta musamman ga wannan canji ya bambanta bisa ga mataki na janyewa da kuma hanyar gudanar da mulki; 10-21 kwanakin da za a janye daga gwargwadon wucewa da kuma kai-tsaye GluR2-dauke da masu karɓa na AMPA sun kasance suna da alhakin canje-canje a tashar AMPA (Boudreau da Wolf, 2005; Boudreau et al., 2007; Kourrich et al., 2007; Ferrario et al., 2010) yayin da fiye da kwanaki 21 GluR2-rasa masu karɓa na AMPA suna kara zuwa synapses. Sakamakon binciken ƙarshe shine ya zama lamarin ne kawai lokacin da ake amfani da cocaine (Conrad et al., 2008; McCutcheon et al., 2011), ko da yake duba (Mameli et al., 2009). Bisa ga karuwar hali na GluR2-rashin masu karɓar AMPA yana iya zama cewa sanya su ya zama a mayar da martani ga bakin ciki na NAc da aka haifar da ciwon kai na cocaine, sabili da haka hakan ya haifar da karuwar karɓar MSN zuwa abubuwan da ke haifar da hawan cocaine a nan gaba. Babu shakka, hana GluR2-rashin masu karɓa na AMPA a cikin NAc ya hana magana akan ƙwayar cocaine wanda aka kafa a ciki (Conrad et al., 2008), da kuma neman hanyar cocaine ta hanyar AMPA ko cocaine kuma an katange shi ta hanyar injections na oligonucleotides antisense na GluR1 mRNA a cikin NAc (Ping et al., 2008).

Drug gwagwarmaya bayan janyewar sake mayar da synaptic yiwuwar zuwa ciki

Ƙarawa a ƙarfin synaptic da kuma bayyana yanayin fuska na ƙungiyar ta AMPA ta hanyar kwantar da hankali ta hanyar cocaine a cikin NAc bayan da aka janye daga gwamnati ba tare da kwakwalwa ba a baya ya sake komawa kan aiwatar da inganci na cigaban cocaine (sake ƙalubalanci) (Thomas et al., 2001; Boudreau et al., 2007; Kourrich et al., 2007; Ferrario et al., 2010). Sabili da haka, an sake jijiyar ɓarna a cikin ginin NAC lokacin da aka auna 24 h bayan wannan ingancin cocaine (Thomas et al., 2001), ko da yake duba (Pascoli et al., 2012). Abin takaici wannan yana nufin ya daidaita tare da furcin mahimmanci, kuma a cikin yanayin amphetamine akalla, an nuna shi a matsayin wanda aka lalata kuma yana dogara ne a kan endocytosis na GluR2 na masu sauraron AMPA (Brebner et al.), 2005). Rage a cikin bayyanar fuska na masu sauraron AMPA bayan yunkurin maganin cocaine ya kasance kamar yadda a cikin 7 kwanakin bayanan yanayi ya dawo zuwa matakan da aka kwatanta da ratsan hawan cocaine-pretreated (Ferrario et al., 2010). Saboda haka, yana nuna tarihin maganin cocaine da kuma janyewa zai iya canza canjin synaptic filastik a cikin NAc.

An danganta haɗin kai tsaye a cikin kwanan nan tsakanin yiwuwar haɗin ƙwayar cortico-collapses akan D₁ Kwayoyin masu karɓar raguwa waɗanda ke bin 7 kwanakin janyewa da kuma nuna mahimmanci. Kamar yadda aka ambata a baya, bayan 7 kwanakin janye daga mulki guda daya na cocaine, waɗannan haɗin suna samuwa su kasance masu tasowa a tsakiya da harsashi (kamar yadda aka ƙaddara ta karuwa a amplitude mEPSC) kuma HFS ya ragu. Ba a samo wannan ba don synapses akan D₂ Kwayoyin masu karɓar raguwa (Pascoli et al., 2012). Lokacin da ya sake komawa optogenetically a vivo ta hanyar yarjejeniyar da aka sani don haifar da LTD, ƙungiyar cortico-accumula synapses on D₁-ananan kwayoyin halitta sun nuna yawan mEPSC da ragewa da aka nuna ma'anar locomotor. Abin mahimmanci, iyawar HFS don kawo LTP an mayar da ita ga waɗannan na'urori (Pascoli et al., 2012), don haka nuna alamar kai tsaye tsakanin wannan maganin synaptic na musamman a ɓangaren cortico-accumulation synapses da kuma nuna mahimmanci ga cocaine.

Rashin ciwo a cikin nauyin na NAc yana da rinjaye a kan rikice-rikice zuwa tsangwama

Kamar yadda aka ambata a sama, yana nuna cewa cocaine yana haifar da canje-canjen matakan gyaran ƙwayoyin na NAC MSNs. Kalmar "rubutun kalmomi" Ibrahim da Bear sunada su ne da farko don su bayyana canji a cikin ikon yin amfani da synapses don su sami ladabi na gaba (Ibrahim da Bear, 1996). Saboda haka, hasara na LTD ana kiyaye shi a duka nauyin NAC da harsashi na 24 h bayan ƙarshen kulawa da kansa na cocaine; duk da haka bayan 21 kwanakin rashin daidaituwa wannan lalacewar ke samuwa ne kawai a cikin zuciyar (Martin et al., 2006). Irin wannan kasawar ba a samo shi a cikin dabbobi da dabbobi da ke da kayan abinci ba, wanda ya nuna shi ya zama daidai da tsarin kula da hakar gwiwar da ake son kai tsaye ba tare da hade da ilimin aikin injuna ba ko halayyar cocaine da se (Martin et al., 2006), thus yana iya yiwuwa yiwuwar maganin maganin miyagun ƙwayoyi a cikin NAC na iya haifar da sauyi daga saurin amfani da shi don halayyar magungunan miyagun ƙwayoyi. Rashin rashin lafiya a cikin NAc da aka haifar da ciwon gine-ginen cocaine na iya nunawa a cikin magungunan magungunan ƙwayoyi kamar rashin iyawa don hana halayyarsu kuma ta hana hana amfani da miyagun ƙwayoyi.

m a vivo gwaje-gwaje na electrophysiological goyon bayan wannan jumlar. An yi amfani da cocaine mai gudanarwa wanda ya biyo bayan horo ta ƙyama don haifar da ƙananan ƙira wanda ya sa ikon PFC ya ƙarfafa don samar da LTP ko LTD a cikin MSNs na NAc (Moussawi et al., 2009). Bugu da ƙari, gwamnati na N-acetylcysteine, wani magani da ke daidaita ka'idodin gwal da kuma rage sha'awar addicts (Amin et al., 2011), an samo don warware wannan maganin maganin cocaine da kuma haifar da ikon yin LTP ko LTD (Moussawi et al., 2009). Wadannan binciken sun kara zuwa samfurin dabba na komawa, tsari na sake dawowa (duba Tebur Table1).1). An nuna jiyya tare da N-acetylcysteine don sake dawowa da yaduwar kwayoyi da aka samu ta hanyar kaya ko Firayim, wani sakamako wanda ya ci gaba da kasancewar 2 bayan mutuwar magani. Abu mai mahimmanci, wannan haɓaka ya danganta da ikonsa na mayar da ƙarfin haɗin gwiwa ga haɗin gwiwar cortico-collapses (Moussawi et al., 2011).

TBayanan da ke tattare da halayen yana samar da dangantaka mai haɗari tsakanin halayyar cocaine-induced filasti a cortico-accumulation synapses da kuma yiwuwar sake koma baya, daidai da tsarin glutamate ka'idar homesetas na buri. Saboda haka, rashin nasarar PFC don sarrafa dabi'un hawan miyagun ƙwayoyi za a iya danganta su da rashin daidaituwa tsakanin synaptic da non synaptic glutamate (Kalivas, 2009). Hanyoyin maganin cocaine na yau da kullum ya haifar da rage yawan matakan da ake amfani da shi a cikin ƙaddamarwa ta hanyar ƙaddamar da ƙwayar mafitar cystine-glutamate. Wannan yana ɗauke da sauti daga masu karɓar mGlu2 / 3 mai mahimmanci wanda ke samuwa a synapses na cortico-striatal wanda yakan yi aiki don iyakance izinin glutamate (Kalivas, 2009). N-acetylcysteine ya hana yin amfani da miyagun ƙwayoyi ta hanyar kunna mai musayar cystine-glutamate, don haka ya kara karfin daɗaɗɗen maɗaukakawa da masu karɓar mGluR2 / 3 mai mahimmanci don rage sakin glutamate da ke hade da neman magani (Kalivas, 2009). Bisa ga haɗin mai karfi tsakanin tsarin mGluR2 / 3 na sasauran synaptic glutamate da kuma neman ƙwayoyi, karfin mGluR2 / 3 wanda ya hana maimaita N-acetylcysteine na LTP daidai ne da yiwuwar daidaita tsarin ƙwayoyin cortico-accumulation yana ingantawa a cikin sake dawowa (Moussawi et al., 2009).

Ƙarin shaidar da ke taimakawa ga mahimmanci ga gyaran da aka yi a NAc glutamatergic da ke haɓaka cikin halayen miyagun ƙwayoyi yana samuwa ta hanyar lura cewa tsarin kula da GluR2-rashin masu kula da AMPA wanda ke kulawa da kwantar da hankalin cocaine wanda aka gani bayan an cire ta daga cocaine (Conrad et al., 2008), da kuma rushe cinikayya na GluR2-dauke da masu karɓa na AMPA a ko dai ma'anar NAC ko harsashi wanda ke haɓaka haɗin cocaine don sake dawo da lalata ƙwayoyin cuta (Famous et al., 2008). Kasuwancin AMAP mai karɓa na watsa shirye-shiryen ya bayyana ya dace sosai ga neman magani. Saboda haka, gwamnatin tsakiya mai kula da agonist ta AMPA ta inganta yayin da abokin taƙama ya hana cocaine-neman (Cornish da Kalivas, 2000) da kuma irin wannan sakamakon da aka samu ga jaridar heroin (Lalumiere da Kalivas, 2008) da barasa (Backstrom da Hyytia, 2004). Lalle ne, ƙaddamar da watsa shirye-shirye ta AMPA daidai ne da wani muhimmin tasiri ga sakin kaya na farko da aka sanya a cikin magungunan kula da miyagun ƙwayoyi (McFarland et al., 2003; Kalivas et al., 2005).

Bisa ga wannan matsayi na musamman don ƙaddamar da ƙwarewar AMPA a cikin halayen haya-ƙwayoyi, ba abin mamaki bane cewa an sake dawowa da buƙatar heroin a cikin berayen da aka nuna a kwanan nan ya buƙaci ƙarfin LTP kamar ƙarfin synaptic a cikin haɗin gwiwar cortico-colnapses (Shen et al ., 2011). Wannan karuwa a ƙarfin synaptic yana tare da canje-canje a gyaran gyare-gyare kuma an buƙata ka'idojin ƙaramin NR2B na mai karɓar NMDA (Shen et al., 2011). Ƙarin nazarin nazarin maganin synaptic sakamakon sakamako na miyagun ƙwayoyi idan ba tare da samfurin likitoci ba zai ba da hankali ga ainihin canji na synaptic wanda ya samo asali ta hanyar samo maganin miyagun ƙwayoyi.

Ta hanyar nazarin sauye-sauye na synaptic a cikin tsarin yanayin ciwon kai na yau da kullum da halayen miyagun ƙwayoyi bayan rashin lalacewa ko abstinence, yana da mahimmanci cewa sakamakon gwaji zai nuna misalin canje-canje da ke faruwa a cikin ƙwayar magungunan miyagun ƙwayoyi maimakon akasin kasancewar sakamakon maganin miyagun ƙwayoyi kawai. Duk da haka, yayinda yake nuna cewa gwamnati ta shawo kan sauyawar canji a canjin synaptic, ba a sani ba ko waɗannan su ne waɗanda ba a ba da takamaiman abubuwan da ke faruwa a duk waɗanda aka fallasa da kwayoyi ba, ko kuma wadannan sauye-sauyen sun faru ne musamman a cikin ƙwararrun mutane masu tasowa. Ayyukan wa'azi daga gine-ginen Piazza sunyi wannan tambaya ta hanyar kwatanta sasauran synaptic a cikin NAc na berayen da aka lasafta su a matsayin "mai shan tabarba" ko "marasa shan magani" ta yin amfani da ka'idojin DSM-IV (Kasanetz et al., 2010). An kirkiro ratsi masu kula da kansu na cocaine a matsayin "masu haɗari" idan sun nuna matsala wajen rage yawan ciwon hawan cocaine, haɓaka ƙaruwa don neman cocaine da ci gaba da amfani duk da sakamakon da ya faru. An gano cewa bayan kwanaki 17 na gine-ginen hawan cocaine, raunuka "mai shan magani" da "raunin shan taba" sun nuna maye gurbin LDD mai kwakwalwa a cikin NAc. Bayan kwanakin 50 na gine-ginen hawan cocaine, an mayar da LDD mai kwakwalwa mai kwakwalwa ta DND a cikin ratsan "marasa shan magani", amma wadannan lalacewar sun kasance a cikin ratsan "masu shan kishi", duk da rashin bambancin yawan cocaine waɗannan kungiyoyi biyu sun bayyana a Kasanetz et al. (2010). Wadannan gwaje-gwajen sun bada hujja mai karfi cewa maye gurbin zuwa tsangwama zai iya haɗuwa da wani nau'i na "anaplasticity," ko rashin iyawa don magance rashin lalacewar miyagun ƙwayoyin cuta a cikin haɗin gizon synaptic.

Tabbatacce ne daga shaidar da aka gwada a sama da abin da ake nunawa ga magungunan zalunci na iya haifar da canje-canje mai dorewa a ƙarfin synaptic a cikin jihohin kwakwalwa da kuma hanyoyin da aka haɗa da ladaran magani (Hyman et al., 2006; Kauer da Malenka, 2007; Kalivas da O'Brien, 2008; Luscher da Malenka, 2011). Bugu da ƙari, VTA da NAc, an yi amfani da gyaran maganganu na synaptic a lokacin da ake nunawa ga magungunan wasu sassa na tsarin na mesolimbic ciki har da PFC, gado na launi na tsakiya da tsakiya amygdala (Dumont et al., 2005; Fu et al., 2007; Van Den Oever et al., 2008). Duk da haka, idan aka ba da binciken da ke sama an nuna cewa ƙananan ƙarancin gaɓoɓin ƙwayoyin cuta na MSN sun fi dacewa da jaraba a cikin mutane.

Ka tafi zuwa ga:

Tsarin littattafai na yin amfani da ƙwayoyin cuta

Yayin da yake a fili cewa kwayoyi na cin zarafi sun iya canza sakon synaptic a cikin tsarin mesocorticolimbic, don gyaran gyare-gyare a cikin aikin neuronal da za a cimma, de novo ana buƙatar haɗin gina jiki (Kandel, 2001). Hakika, maimaitawar tasirin abin da ke nuna magungunan miyagun ƙwayoyi a cikin yanki na musamman a cikin ƙididdigar ɗan adam kuma an tsara shi cewa waɗannan canje-canjen na iya haifar da wasu abubuwan rashin halayen halayen da suke nuna jaraba (McClung da Nestler, 2003; Chao da Nestler, 2004). Akwai hanyoyi masu yawa wanda magungunan ƙwayoyi suke iya tsara tsarin jinsin mutum, ciki har da kunnawa da kuma kawar da abubuwan sakonnin, wanda ya haifar da cututtuka da kuma shigar da RNA.

Bayanan rubutun

Bayanan sakonnin sunadaran sunadarai ne wadanda suke ɗaukar takaddama akan DNA don tsara fassarar kwayar halitta ta hanyar hulɗa da RNA polymerase II (Mitchell da Tjian, 1989). Ana iya haifar da abubuwan da za a iya fassarawa ko kuma a mayar musu da martani don magance matsalolin muhalli, wanda zai haifar da canje-canje a fannin nunawa da kuma kyakkyawan aikin neuronal. An gano wasu dalilai na sassaucin ra'ayi don tasirin su a cikin jaraba saboda maganganun su da kunnawa su ne aka tsara su a cikin hanya ta mesocorticolimbic a kan yadawa ga magunguna. ΔFosB yana ɗaya daga cikin ƙididdigar takardun izinin da aka samu ta musamman saboda matsayi na musamman. ΔFosB wani nau'i ne mai sauƙi na FosB, kuma yana ba da homology tare da wasu 'yan uwa na Fos ciki har da C-Fos, FosB, Fra1, da Fra2 wadanda duk sunyi amfani da sunadaran iyali na Jun (c-Jun, JunB, ko JunD) abubuwan haɓakaccen kayan aiki-1 (AP-1) bayanai (Morgan da Curran, 1995). Wadannan 'yan uwan Fos suna jawo hanzarin hanzari a cikin sakonni saboda amsa rashin lafiya ga marasa lafiya, duk da haka saboda rashin lafiyar wannan maganganu yana da tsayuwa kuma ya dawo zuwa matakan basal cikin sa'o'i (Graybiel et al., 1990; Young et al., 1991; Fata da al., 1992). Hakanan, ΔFosB yana tarawa a cikin magungunan bayan bin doka ta miyagun ƙwayoyi, kuma maganganunsa na cigaba da makwanni da dama bayan da aka kwantar da kwayar cutar ta karshe (Hope et al., 1994; Nye et al., 1995; Nye kuma Nestler, 1996; Pich et al., 1997; Muller da Unterwald, 2005; McDaid et al., 2006). Bayanai daga nazarin halayen suna taimakawa ga ΔFosB a wasu daga cikin lalacewar da ake amfani da kwayoyi. Sakamakon maganin ΔFosB a sakamakon da aka haifar da ƙara yawan halayen locomotor ga magunguna mai tsanani da na kullum, kuma yana ƙarfafa kayan haɓaka na cocaine da morphine (Kelz et al., 1999; Colby et al., 2003; Zachariou et al., 2006), alhali kuwa hanawa na ΔFosB yana haifar da sakamakon halayen (Peakman et al., 2003). Dangane da ikon da ya haifar da kyawawan dabi'u na magungunan ƙwayoyi, an ƙaddamar da wannan ƙididdigar lissafi don wakiltar "canza kwayoyin" wanda zai taimaka wajen canzawa zuwa jaraba (Nestler, 2008).

FAMP mai amsa sinadarin sinadaran (CREB) wani abu ne na ƙididdiga wanda aka mayar da hankali ga ƙididdigar yawan bincike saboda matsin da yake da shi wajen yin amfani da kwayoyi (McPherson da Lawrence, 2007). An bayyana CREB sau da yawa a cikin kwakwalwa, kuma ana iya kunna shi ta hanyar yawan hanyoyi na sigina na intracellular wanda ya ƙare a cikin phosphorylation a serin 133 (Mayr da Montminy, 2001). CREB mai lafazin (pCREB) yana ƙarfafa aikin daukar nauyin gina jiki na CREB (CBP) wanda ke taimakawa wajen rubutun da wasu kwayoyin halitta masu rai (Arias et al., 1994). PCREB yana hanzari da sauri a cikin striatum a yayin da ake nunawa ga psychostimulants (Konradi et al., 1994; Kano et al., 1995; Walters da Blendy, 2001; Choe et al., 2002) kuma wannan shi ne tsinkaye don wakiltar wata hanyar da za ta taimaka wajen magance magunguna (McClung da Nestler, 2003; Dong et al., 2006). Daidai da wannan, cin zarafi na CREB a kwamin na NAc ya rage dabi'un kaya na cocaine a cikin tsari na musamman (CPP), yayin da aka lura da abin da aka hana a kan hana CREB a wannan yankin (Carlezon et al., 1998; Pliakas et al., 2001). Hakazalika, ƙwayoyin cututtuka ko ƙyama ga CREB a dorsal striatum ya ba da hankali ga abubuwan da ke kunshe da halayen magungunan ƙwayoyin cuta, suna ƙara ƙarin goyon bayan wannan ra'ayin (Fasano et al., 2009; Madsen et al., 2012).

Duk da yake bayanai daga gwaje-gwaje na CPP sun goyi bayan ra'ayin CREB a matsayin mai amfani da magungunan magani, akalla game da cocaine, wannan yana iya zama mai zurfi. Yawan karatu da amfani da wasu fasahohi don canza aikin CREB a cikin harsashin NAC sun nuna cewa hanawa CREB ta rage karfin hawan cocaine a cikin tsarin mulkin kai (Choi et al., 2006; Green et al., 2010; Larson et al., 2011), yayin da karfafa hawan cocaine ya kara inganta ta hanyar CREB overexpression a wannan yanki (Larson et al., 2011). Wadannan binciken masu banbanci suna yiwuwa ne saboda muhimmancin bambancin dake tsakanin ka'idodin kayan aiki da na Pavlovian da na son rai vs. Gwamnatin miyagun ƙwayoyi. Cibiyar ta CPP ta ƙunshi matakan haɗin gwiwar shiryawa, kuma an yi la'akari da ita a matsayin nauyin da ba a kai ba daga cikin abubuwan da ake amfani da su a magani maimakon maganin miyagun ƙwayoyi da se (Bardo da Bevins, 2000). Za a iya rinjayar da kai ga tsarin kula da miyagun ƙwayoyi na son rai da dama daga abubuwan da ke motsa jiki, da kuma damar CREB aiki a NAc don rage martani ga matsalolin tashin hankali (Barrot et al., 2002) da kuma halin haɓaka mai zurfi (Pliakas et al., 2001) zai iya rinjayar haɓaka ga miyagun ƙwayoyi. Abin sha'awa, rago daga CREB daga PFC yana haifar da ƙaddamar da motsi don maganin maganin cocaine (McPherson et al., 2010), yana nuna cewa tasiri na gyaran CREB a kan hali kuma ya bambanta ga yankuna daban-daban na kwakwalwa. Wannan watakila ba abin mamaki bane cewa Kundin CREB ya bambanta da alama bisa ga tsarin salula (Cha-Molstad et al., 2004) kuma zai zama mahimmanci a gane da canje-canje a cikin layin jigilar kalma wanda ke gudana ƙarƙashin rabuwa na CREB da ke taimakawa ga waɗannan samfurori. Har ila yau, abubuwa masu tasowa sune kallon cewa CREB a cikin gurbin NAc yana da mahimmanci ga CPP (Nicotine CPP) (Brunzell et al., 2009), suna nuna cewa sunadaran da ke da nasaba da nauyin nicotine sun bambanta daga wadanda ke da magungunan cocaine da morphine, wadanda suka haɓaka ta hanyar CREB a cikin nauyin NAC (Carlezon et al., 1998; Pliakas et al., 2001; Barrot et al., 2002).

Tsarin halittu

Magungunan Epigenetics yana da wasu ma'anoni, amma a cikin neuroscience an bayyana shi azaman canje-canje a cikin furcin kalma wanda ke faruwa ta hanyar canzawar chromatin wadda ba a kawo ta ta canje-canje a jerin jigidar halittar DNA (McQuown and Wood, 2010). Chromatin ya bayyana yanayin DNA lokacin da aka kunshi shi cikin tantanin halitta. Kullin maimaitawa na chromatin shine ƙwayar halitta, wanda ya ƙunshi nau'in nau'i na DNNUMX nau'in DNA wanda aka haɗe a kusa da octet wanda ya ƙunshi nau'i na nau'ikan tarihin hudu (H147A, H2B, H2, da H3) (Luger et al., 1997). Hannun amino na wadannan tarihin tarihi zasu iya shawo kan gyare-gyare na bayanan fassara ciki har da acetylation, methylation, phosphorylation, ubiquitination, da sumoylation (Berger, 2007). Bugu da žari da kuma cire wadannan kungiyoyi masu aiki daga tarihin histone ana aiwatar da su ta hanyar adadin abubuwa masu yawa na histone, wanda ya hada da acetyltransferases, deacetylases, methyltransferases, demethylases, da kinases (Kouzarides, 2007). Wadannan sauye-rubuce na tarihi suna nuna alamar daukar nauyin takardun rubutu da sauran sunadarai da ke cikin ka'idojin rubutu, da kuma canza tsarin tsarin chromatin don sanya DNA mafi mahimmanci ga kayan aiki na rubutu (Strahl da Allis, 2000; Kouzarides, 2007; Taverna et al., 2007). Hanyoyi na asalin halitta suna nuna mahimmancin hanyar da matakan yanayi zasu iya tsara jigilar mutun da kuma kyakkyawan hali.

Kwanan nan, an tabbatar da gyare-gyare na chromatin a matsayin wani muhimmin ma'anar ƙwayoyin cuta da ke haifar da ƙwayoyin cuta da kuma halayyar (Renthal da Nestler, 2008; Bredy et al., 2010; McQuown da Wood, 2010; Maze da Nestler, 2011; Robison da Nestler, 2011). Shaida ta farko ta wannan daga daga gwaje-gwajen da Kumar da abokan aiki suka yi sunyi amfani da jarabawar chromatin immunoprecipitation (ChIP) don nuna cewa cocaine na haifar da gyaran tarihi a wasu masu tallafawa na musamman a cikin striatum (Kumar et al., 2005). Musamman, rashin kulawar maganin cocaine ya haifar da H4 hyperacetylation na cFos promoter, alhãli kuwa mulkin na yau da kullum haifar da H3 hyperacetylation daga BDNF da kuma Cdk5 masu tallatawa. Tarihin acetylation ya kunshi canzawa na enzymatic na ƙungiyar acetyl zuwa wutsiyar N-terminal ta tarihi, wanda ke kawar da hulɗar electrostatic tsakanin histone da mummunan cajin DNA, yana mai sauƙaƙa shi zuwa kayan aikin rubutu (Loidl, 1994). Wannan ya dace da haɗin cocaine don ƙara yawan kalmomi na Fos iyali a cikin layi (Graybiel et al., 1990; Young et al., 1991), alhali kuwa BDNF da Cdk5 suna ci gaba ne kawai a kan abin da ke faruwa a kullum (Bibb et al., 2001; Grimm et al., 2003).

Za a iya samun magungunan histone de hyperacetylated ta hanyar gwaji ta hanyar gudanar da magungunan histone deacetylase (HDAC), kuma an yi amfani da wadannan kwayoyi don nazarin tasirin karuwa a duniya a cikin tarihin acetylation a kan maganganun halayyar maganin magunguna. Gudanar da tsarin kula da masu kwakwalwa na HDAC da yawa ya haɓaka hyperacetylation a cikin maganin cocaine a cikin striatum (Kumar et al., 2005), kuma wannan halayen hawan cocaine ya haifar da locomotion da sakamako na cocaine (Kumar et al., 2005; Sun et al., 2008; Sanchis-Segura et al., 2009). Hannar HDAC na iya ƙara haɓaka ƙaƙƙarfan locomotor zuwa ethanol da morphine, da kuma sauƙaƙe morphine CPP (Sanchis-Segura et al., 2009), Duk da haka, an hana gano masu hana masu kwakwalwa ta HDAC don hana haɓakawa ga abin da yake nunawa ga mutum guda (Jing et al., 2011), da kuma rage dalili don kulawa da sanyaya ta jiki (Romieu et al., 2008). Wadannan binciken da ya bambanta na iya nuna bambancin da ke cikin sharuɗɗa na gwamnati, kuma yana da mahimmanci sun nuna cewa masu hanawa na HDAC ba su da karfin hali na halayya ga kwayoyi a duk yanayin.

Dangane da tasirin da suke yi akan kundin gwanin, masu hanawa na HDAC sunyi aiki don sauƙaƙe wasu nau'o'in ilmantarwa (Bredy et al., 2007; Lattal et al., 2007). An nuna a kwanan nan cewa gwamnati mai hanawa ta HDAC bayan sake sakewa zuwa wani yanayi na haɗin cocaine wanda ya haɗu da shi zai iya sauƙaƙe yawan CPP mai kwakwalwa, kuma wannan yana yiwuwa ya danganci karin tarihi na H3 acetylation a NAc (Malvaez et al., 2010). Jiko na mai hana suraroylanilide hydroxamic acid (SAHA) a cikin NAC a lokacin kwanciyar hankali na CPP tana ƙarfafa sakamako na cocaine (Renthal et al., 2007), yana nuna cewa dakatarwar HDAC a wannan yanki na iya sauƙaƙe duk abin da ya shafi ilmantarwa da kuma ilmantarwa, dangane da mahallin da aka yi amfani da miyagun ƙwayoyi. Ƙarin gwaje-gwaje sun nuna rawar da za a takawa ga HDAC5, kuma mai girma HDAC ya bayyana sosai a cikin NAc a cikin sauyewar sakamako na cocaine. Cibiyar Cocaine ta kara aiki ta hanyar HDAC5 ta hanyar sarrafa tsarin da take ciki da kuma samar da makaman nukiliya na gaba, kuma dephosphorylation na HDAC5 a cikin NAc ya ɓatar da ci gaban cocaine CPP (Taniguchi et al., 2012). Hakazalika, yawancin maganganu na HDAC5 a cikin NAc a lokacin kwanakin kwastar na CPP yana karɓar ladabi na cocaine, kuma wannan sakamako yana juyawa a kan bayyanar nau'i na mutunci na HDAC5 a cikin NAc (Renthal et al., 2007). Yana yiwuwa HDAC5 yana aiki da waɗannan abubuwa ta hanyar hana yin amfani da kwayoyin halitta wanda ya haifar da miyagun ƙwayoyi wanda yakan kara yawan kaya na cocaine.

Binciken cikakkiyar tsarin gyaran chromatin da ke faruwa a cikin NAC saboda sakamakon yaduwar cutar cocaine ya nuna yawanin gyare-gyare na chromatin a yankuna masu tallafawa na ginsunan jini na duka CREB da ΔFosB (Renthal et al., 2009). Wannan bincike kuma ya saukar da ka'idoji na sirri guda biyu, SIRT1 da SIRT2, waxanda sunadarai ne wadanda ke da aikin HDAC kuma suna iya samun adadin sunadarin sunadarai na dacetylate (Denu, 2005). Sakamakon SIRT1 da SIRT2 suna haɗuwa da haɓaka H3 da yawa da kuma ƙaruwa na ΔFosB a masu samar da layi, suna nuna cewa sune makomar ΔFosB (Renthal et al., 2009). Tsarin tsari na SIRT1 da SIRT2 an yi zaton suna da halayen hali; sirtuins rage karuwa na NAc MSNs a vitro, da kuma maganin maganin maganin maganin maganin maganin cocaine, yayin da haɓakawa ya kara yawan amsoshin maganin cocaine (Renthal et al., 2009).

Bugu da ƙari, aikin da ake gudanarwa ga HDAC, binciken nazarin halittu ya nuna wani muhimmin tasiri ga histone acetyltransferases (HATs) a cikin sasanta wasu daga cikin maganganun da aka yi wa magunguna. Tabbatacciyar hanya mafi mahimmanci wadda CBP ke iya inganta ingantacciyar sakonni ta hanyar aikin HAT na ciki (Bannister and Kouzarides, 1996), kuma binciken da aka yi a kwanan nan ya shafi aikin HAT na CBP a wasu daga cikin cututtukan epigenetic da suka haifar da yuwuwar miyagun ƙwayoyi. Dangane da cututtukan cocaine, an tattara CBP zuwa ga FosB mai talla inda yake acetylates histone H4 da kuma ƙara fadin FosB (Levine et al., 2005). A cikin ƙananan ƙananan yara na CBP, ƙananan CBP ne aka tattara zuwa ga mai talla wanda zai haifar da rage yawan tarihi na histone da FosB. Wannan kuma ya dace da ƙananan ƙungiyar ΔFosB a cikin striatum, kuma ba abin mamaki bane waɗannan ƙwayoyin suna nuna raƙuman ƙwarewa a sakamakon maganin cocaine (Levine et al., 2005). Kwanan nan, ta amfani da tsarin recombination na cre-lox Malvaez da abokan aiki sun binciko muhimmancin ayyukan CBP da ke musamman a cikin NAC akan rubutun gwanon halayyar hawan cocaine (Malvaez et al., 2011). An ruwaito cewa an yi niyyar cirewa daga CBP a cikin NAc ya haifar da rage tarihi na acetylation da c-Fos expression, kuma ya hana aikin hawan locomotor don amsawa ga magungunan cocaine mai tsanani da na yau da kullum (Malvaez et al., 2011). Har ila yau, an hana karbar cocaine mai kwakwalwa a cikin wadannan ƙananan ƙuƙuka, suna ba da shaida ta farko cewa aiki na CBP a cikin NAc yana da mahimmanci don samarda tunanin tunawa da miyagun ƙwayoyi (Malvaez et al., 2011).

Kwanan nan, gwaje-gwajen daga dakin gwaje-gwaje na Kandel sun bayyana cewa hanyoyin halittar asali na iya haifar da tasirin tunanin nikotin na aiki a matsayin "maganin ƙofa". Mice tare da nicotine kafin yaduwar maganin cocaine ya nuna ingantaccen haɓakar locomotor da ladaran cocaine idan aka kwatanta da ƙananan ƙwayoyin nicotine (Levine et al., 2011). Bugu da ƙari, ƙaddamar da ƙwayar nicotine ya haifar da ciwon haɓakar hawan cocaine da ke ciki na LTP a cikin haɗin gwaninta a cikin NAc, abin da ba a gani ba tare da nicotine kadai. Bincike na gyaran tarihi na tarihi na 7 ya nuna cewa H3 da H4 acetylation suka karu. FosB mai tallatawa a cikin bugun jini, sakamakon da ba a faɗi shi ba don mayar da martani ga gwamnatin cocaine ta kwana 7. Ayyukan HDAC sun ragu a cikin ƙwayar berayen da aka kula da nicotine, amma ba canzawa a cikin berayen da aka kula da hodar iblis. Abin mamaki shine, jigilar mai hana HDAC kai tsaye a cikin NAc ya iya kwaikwayon sakamakon gurɓataccen maganin nicotine a cikin tasirin tasirin cocaine. Babu ɗayan waɗannan canje-canje da aka lura lokacin da aka bi da beraye tare da hodar iblis kafin nicotine, yana mai tabbatar da ƙayyadadden yanayin waɗannan tasirin. Wannan kyakkyawan tsarin gwajin ya samar da cikakken bayani game da dalilin da yasa shan taba sigari kusan koyaushe yana gab da amfani da hodar iblis a cikin ɗan adam (Kandel, 1975; Kandel et al., 1992).

Baya ga histone acetylation, histeth methylation kuma a kwanan nan an gane shi a matsayin hali na dacewa chromatin gyara ta hanyar maganin magunguna (Laplant et al., 2010; Maze et al., 2010, 2011). Methylation histone ya ƙunshi ƙarar enzymatic na daya, biyu, ko uku ƙungiyar methyl zuwa rassan lysine ko arginine a N-mota na wutsiyoyin histone, kuma an hade da ko dai kunnawa ko danniya, dangane da yanayin gyara (Rice da Allis , 2001). Nazarin farko don bincika nazarin methylation da aka haifar da cocaine ya jagoranci ganewa na biyu histone methyltransferases, G9a da G9a-kamar furotin (GLP), waɗanda aka ƙaddamar da su a cikin NAc 24 h bayan biyun halayen cocaine ba tare da yadawa ba da kuma cocaine -addar mulki (Renthal et al., 2009; Maze et al., 2010). An danganta wannan ka'idoji da ragowar irin wannan a cikin histone H3 lysine 9 (H3K9) da kuma 27 (H3K27) methylation. Bayan haka, an nuna G9a overexpression a cikin NAc don rage yawan maganin ciwon hawan cocaine wanda aka zaba ta hanyar CPP, kuma ya hana ƙãra a yawan tsabar tsabar tsabar tsabar mahaifa wanda aka saba da shi don amsa yawan maganin cocaine (Maze et al., 2010). Hakan ya faru a yayin da aka hana G9a magana a cikin NAC, sakamakon hakan ya haifar da karuwar tsabar dindritic spinritic da kuma sakamako na cocaine inganta. Akwai tabbacin cewa canza canjin cocaine a G9a magana da kuma ragewa a H3K9 da H3K27 an tsara ta ta ΔFosB (Maze et al., 2010). Gaba ɗaya, waɗannan gwaje-gwaje sun nuna muhimmancin rawar da G9a ke yi a tarihi a cikin wasu dogon lokaci da halin da ake ciki da kuma biochemical sakamakon lalatawa zuwa cocaine.

Kwanan nan, gyaran tarihin H3 lysine 9 (H3K9me3) wanda aka yi la'akari da shi a matsayin alamaccen heterochromatic alama, an nuna cewa an tsara shi a cikin NAC ta hanyar yaduwar cutar cocaine mai tsanani (Maze et al., 2011). Maganar cocaine ta sake haifar da raguwar ragewa a cikin H3K9me3 ɗaukar nauyin da aka haɓaka musamman a cikin yankuna masu ƙwayoyin halitta (Maze et al., 2011). Wadannan binciken farko sun nuna cewa yaduwar karfin maganin cocaine mai yawa zai iya haifar da rashin daidaituwa ga wasu abubuwa masu juyowa a cikin naurorin Nec na NAc, kuma zai zama babban sha'awa don gano irin sakamakon da wadannan sababbin halittu suka haifar.

Bisa ga yanayin jurewa na har abada, bincike na baya-bayan nan ya gano ma'anar DNA methylation, wanda ya fi dacewa da tsarin gurbin asalin halittar mutum idan aka kwatanta da gyaran tarihi. Halittar halittar DNA ta ƙunshi ƙarin adadin ƙwayoyin methyl zuwa asali na asali a cikin DNA, kuma ana danganta shi da matsalolin rubutu (Stolzenberg et al., 2011). Binciken dabarar hanzarin berayen da suka karu da hawan cocaine a kan kwanakin 7, ko kuma cocaine wanda ake gudanarwa a kan kwanakin 13 sun bayyana ka'idojin DNA methyltransferase DNMT3A a cikin NAc 24 h bayan bayanan cocaine na ƙarshe (Laplant et al., 2010). Sabanin haka, bin ƙarin hawan cocaine na yau da kullum (duk wanda aka gudanar da shi don 3 makonni ko fiye) da kuma kwanan watan 28, dnmt3a an gano mRNA an inganta shi sosai a cikin NAc (Laplant et al., 2010). Tsarin DNA methylation / DNMT3a musamman a cikin NAc an nuna shi a baya don inganta duka CPP da kuma locomotor da hankali ga cocaine, yayin da akasin haka aka kiyaye bayan da aka yiwa DNMT3a a wannan yankin. Bugu da ƙari, hanawa na DNMT3a a cikin NAc kuma ya hana hawan cocaine-haɓaka ƙãra a dantritic spine density (Laplant et al., 2010). Hakanan har yanzu ba a fahimci halin da ake ciki na gyare-gyaren hawan cocaine ba. Ana nuna cewa an hana ƙin ƙaddamar da ƙwayar spine don rage yawan kaddarorin cocaine (Russo et al., 2009; Maze et al., 2010); duk da haka, wasu binciken sun gano cewa hana yin amfani da spinogenesis yana iya samun sakamako na cocaine (Pulipparacharuvil et al., 2008; Laplant et al., 2010). Yayin da cocaine ya nuna cewa ya haifar da tsari mai mahimmanci da ke tattare da wasu tsararraki na dendritic a kan tafarkin da kuma janyewa (Shen et al., 2009), an nuna cewa waɗannan bambance-bambance na iya dogara ne akan irin nauyin sarƙaƙan ƙwayoyi wanda aka canza (Laplant et al., 2010).

Daga gwaje-gwaje da aka bayyana a nan, ya bayyana cewa tsarin da miyagun ƙwayoyi na mota na kwayoyin halitta yana wakiltar maɓallin mahimmanci wanda ke rinjayar halayyar halayyar maganin kwayoyi da kuma ilmantarwa na sakamako. Wani muhimmin mataki na gaba shi ne gano ko wanene daga cikin wadannan canje-canjen cututtuka sun fi dacewa da yanayin cututtukan mutum. Ba cewa abin da ake nunawa ga magunguna ba shi da isa don samar da "kwari" a cikin mutane da dabbobi, ƙaddamar da tsarin da ke ɗaukar nauyin siffofin jaraba, irin su yin amfani da miyagun ƙwayoyi da kuma sake dawowa zai zama muhimmiyar darajar.

MicroRNAs

MicroRNAs na wakiltar wani mahimman hanyar da magungunan ƙwayoyi za su iya tsara jinsin mutum. MicroRNAs ƙananan ƙananan littattafan RNA ne waɗanda ba su da ikon yin rajistar da suke aiki don hana fassara gwargwadon ƙwayar post-rubuce-rubuce ta hanyar ƙaddamar da yankin 3'-untranslated (3'UTR) (Bartel, 2004). Aikin kwanan nan da ƙungiyar Paul Kenny ta jagoranta ya haifar da gano ƙa'idojin rubuce-rubuce ta microRNAs wanda ke faruwa musamman a cikin beraye tare da faɗaɗa damar gudanar da mulkin cocaine (Hollander et al., 2010; Im et al., 2010). Hanyoyin samun dama ta haifar da tasowa, samfurori masu amfani da miyagun ƙwayoyi waɗanda ake zaton su zama abin tunawa da maganin miyagun ƙwayoyi marasa amfani da ke nuna halayen mutum (Ahmed da Koob, 1998; Deroche-Gamonet et al., 2004; Vanderschuren da Everitt, 2004). A cikin berayen da tarihin samun damar yin amfani da cocaine, microRNA miR-212 ya ƙayyade a cikin dorsal striatum (Hollander et al., 2010), yankin kwakwalwa da ke ci gaba da yin aiki tare da kwarewar miyagun kwayoyi (Letchworth et al., 2001; Porrino et al., 2004). Maganar da aka yi wa lakabi ta hanyar miR-212 a cikin dorsal striatum ya rage dalili don cinye cocaine, amma kawai a ƙarƙashin yanayi mai zurfi (Hollander et al., 2010). Tsarin izinin na miR-212 a cikin wannan yankin ya haifar da komai, kuma ya karfafa gwaninta mai kula da cocaine. miR-212 an jawo shi a sakamakon amsa alamar CREB (Vo et al., 2005), kuma yana aiki da illa ta hanyar yiwuwar aikin CREB (Hollander et al., 2010), yana bayyana hanyar da ake amfani da su ta hanyar littafi wanda miR-212 alama ce ta iya kare kariya daga ci gaba da ciwon hawan cocaine.

Magana game da mahimman rubutun na MeCP2 an ƙaddamar da shi sosai a cikin dorsal striatum na berayen bayan karin damar shiga cocaine (Im et al., 2010). Rushewar aikin MeCP2 a cikin dorsal striatum ya hana karuwa daga yawan miyagun ƙwayoyi da ake gani akai-akai a cikin ratsiyoyi masu zuwa, kuma ya haifar da rashin karuwar amsawa ga cocaine. Ba kamar CREB da ΔFosB ba, MeCP2 ne mai rikodin rubutu, yana yin tasirinsa ta hanyar tattara Hakanan HDAC da sauran mawallafi na sakonni zuwa jigilar kwayoyin halitta (Nan et al., 1998). MeCP2 yayi aiki don magance miR-212 a cikin dorsal striatum a cikin yanayin aiki, kuma yana sarrafa ikon bayyana nau'in ƙananan neurotrophic brain (BDNF), wani sinadaran da ke da tasiri wajen daidaita yanayin halayen hawan cocaine (Horger et al ., 1999; Graham et al., 2007). miR-212 kuma za ta iya mayar da martani ga magance MeCP2, kuma waɗannan masu shigar da rubutu guda biyu suna da hannu cikin aikin rashin daidaituwa na gida (Im et al., 2010).

Wadannan binciken sun nuna mahimmancin tsari na rubutu wanda ke faruwa a sakamakon tsarin kula da miyagun ƙwayoyi, kuma ya bada shawara cewa cinyewar miyagun kwayoyi yana sarrafawa ta hanyar daidaitattun masu adawa da kwayoyin halitta wanda ke aiki don sauƙaƙe ko hana aikin amfani da miyagun ƙwayoyi. Zai zama babban sha'awa don gano ko tsarin na transcriptive ta hanyar miR-212 / MeCP2 yana da hannu akan tsarin "dawo da" a cikin ratsan shan magunguna (Kasanetz et al., 2010), kuma wannan na iya kawo mu kusa da fahimtar abubuwan da suke haifar da rashin lahani da kuma jurewa ga jaraba (Ahmed, 2012).

Ka tafi zuwa ga:

karshe

Bincike a cikin shekaru goma da suka wuce ya ba da hankali game da iyawar kwayoyi na cin zarafi don gyara sakonnin synaptic a cikin mesocorticolimbic da corticostriatal circuits, kuma yanzu muna fara fasalta muhimmancin halin wasu daga cikin wadannan canje-canje. Kwanan nan, farfadowa mai girma na epigenetics ya ba da haske akan wasu hanyoyin da kwayoyi masu cin zarafi suka tsara mawuyacin yiwuwar kwayoyin halitta, don farawa canje-canje a cikin bayyanar nunawa. Wannan binciken ya buɗe wasu hanyoyi masu mahimmanci. Binciken cewa N-acetylcysteine zai iya mayar da gurbin da aka yiwa synaptic da gwanin cocaine ya haifar da shi, kuma ya hana sake dawowa da neman tallafin miyagun ƙwayoyi ga 'yan tawaye (Moussawi et al., 2011). Masu zanga-zangar HDAC suna da hankali ga ikon su na inganta wasu nau'o'in ilmantarwa, da kuma binciken kwanan nan cewa butyrate na sodium zai iya sauƙaƙe yawancin CPP da aka samu a cocaine da kuma sake dawowa daga neman magani ne mai alamar (Malvaez et al., 2010). Wani muhimmin mataki na gaba shi ne a tambayi ikon masu hanawa na HDAC don sauƙaƙe nauyin gudanar da mulkin kai tsaye, wanda yafi dacewa da amfani da miyagun ƙwayoyi masu amfani da kwayoyi a cikin mutane. A ƙarshe, ganewar abubuwan da ke tsara ƙwayar magungunan ƙwayoyi suna amfani dashi a kan matakin synaptic (misali, rashin ci gaba a cikin kwaminonin NMDAR na dogara a cikin NAc) da kuma a kan matakin kwayoyin (misali, alamun alamar sakonni da suka shafi miR-212 da MeCP2) suna kawowa mu kusa da fahimtar hanyoyin da ke aiwatar da juyin juya hali zuwa jaraba (Hollander et al., 2010; Im et al., 2010; Kasanetz et al., 2010). Wadannan karatun sun nuna muhimmancin nazarin canje-canjen neroplastic wanda aka kawo ta hanyar daukar nauyin shan magani na son rai maimakon magungunan miyagun ƙwayoyi. Ƙarawa gaba zai zama da muhimmanci don ƙarin bincike don kunshe da tsarin jagorancin nan wanda ya fi dacewa da yaduwar yanayin da ake gani a jikin mutum.

Rikici na sanarwa mai amfani

Mawallafa sun bayyana cewa an gudanar da binciken ne a cikin babu wata kasuwanci ko kudi da za a iya ɗauka a matsayin mai rikici na sha'awa.

Ka tafi zuwa ga:

References

Ibrahim WC, Bear MF (1996). Metaplasticity: da filayen synptic filastity. Trends Neurosci. 19, 126–130. doi: 10.1007/978-3-540-88955-7_6. [PubMed] [Cross Ref]
Ahmed SH (2012). Kimiyya na yin namun-miyagun kwayoyi. Neuroscience 211, 107-125. Doi: 10.1016 / j.neuroscience.2011.08.014. [PubMed] [Cross Ref]
Ahmed SH, Koob GF (1998). Tsarin daga matsakaici zuwa ciwon magungunan miyagun ƙwayoyi: canzawa a yanayin da yake tsaye. Science 282, 298-300. Doi: 10.1126 / kimiyya.282.5387.298. [PubMed] [Cross Ref]
Amin SL, Piacentine LB, Ahmad ME, Li S.-J., Mantsch JR, Risinger RC, et al. (2011). Maimaita N-acetyl cysteine ya rage karfin cocaine yana neman kwayoyi da kuma sha'awar mutane masu dogara da cocaine. Neuropsychopharmacology 36, 871-878. Doi: 10.1038 / npp.2010.226. [PMC free article] [PubMed] [Cross Ref]
Argilli E., Sibley DR, Malenka RC, Filato Ingila, Bonci A. (2008). Kayan aiki da lokaci lokaci na cocaine-induced dogon lokacin yiwuwar a cikin yankin ventral area. J. Neurosci. 28, 9092-9100. Doi: 10.1523 / JNEUROSCI.1001-08.2008. [PMC free article] [PubMed] [Cross Ref]
Arias J., Alberts AS, Brindle P., Claret FX, Smeal T., Karin M., et al. (1994). Ƙaddamar da kwayoyin halitta da kuma jigilar kwayoyin halitta suna dogara da makaman nukiliya na kowa. Nature 370, 226-229. Doi: 10.1038 / 370226A0. [PubMed] [Cross Ref]
Backstrom P., Hyytia P. (2004). Masu amfani da masu amfani da glutamate glutamate antagonists suna tsara tsarin sake dawowa da hali na neman yadu. Barasa. Clin. Exp. Res. 28, 558-565. Doi: 10.1097 / 01.ALC.0000122101.13164.21. [PubMed] [Cross Ref]
Bannister AJ, Kouzarides T. (1996). Babban haɗin gwiwa na CBP shi ne histone acetyltransferase. Nature 384, 641-643. Doi: 10.1038 / 384641A0. [PubMed] [Cross Ref]
Bardo MT, Bevins RA (2000). Yanayin da aka zaɓa a fili: menene ya kara wa fahimtarmu game da ladaran miyagun ƙwayoyi? Psychopharmacology 153, 31-43. [PubMed]
Barrot M., Olivier JDA, Perrotti LI, Dileone RJ, Berton O., Eisch AJ, et al. (2002). Ayyukan CREB a cikin ginshiƙan da ke haɓaka harshe na gwaninta yana sarrafa halayen halayen halayyar halayen halayen halayyar motsa jiki. Shaida. Natl. Acad. Sci. Amurka. 99, 11435-11440. Doi: 10.1073 / pnas.172091899. [PMC free article] [PubMed] [Cross Ref]
Bartel DP (2004). MicroRNAs: kwayoyin halitta, kwayoyin halitta, inji, da kuma aikin. cell 116, 281–297. doi: 10.1016/S0092-8674(04)00045-5. [PubMed] [Cross Ref]
Bellone C., Luscher C. (2006). Cocaine ta jawo hankalin mai karɓa na AMPA mai juyawa a vivo ta hanyar mGluR-dogon lokacin damuwa. Nat. Neurosci. 9, 636-641. Doi: 10.1038 / nn1682. [PubMed] [Cross Ref]
Benwell MEM, Balfour DJK (1992). Sakamakon magungunan nicotine mai maimaitawa da maimaitawa akai-akai akan dopamine da aikin locomotor. Br. J. Pharmacol. 105, 849-856. [PMC free article] [PubMed]
Berger SL (2007). Harshen hadaddun tsarin tsarin chromatin a lokacin karatun. Nature 447, 407-412. Doi: 10.1038 / nature05915. [PubMed] [Cross Ref]
Beyer CE, Stafford D., Labarai MG, Glowa JR, Steketee JD (2001). Maimaita tsinkaya zuwa ƙananan nau'i na haifar da halayen halayyar halayyar jiki da kuma neurochemical to cocaine a cikin berayen. Psychopharmacology 154, 198-204. [PubMed]
Bibb JA, Chen J., Taylor JR, Svenningsson P., Nishi A., Snyder GL, et al. (2001). Hanyoyin ciwon kwakwalwa na kullum sunadaita ta hanyar Cdk5 mai gina jiki neuronal. Nature 410, 376-380. Doi: 10.1038 / 35066591. [PubMed] [Cross Ref]
Bliss TV, Lomo T. (1973). Tsarin jituwa na tsawon lokaci na watsawa na synaptic a cikin gefen katako na gurbin zubar da hanzari bayan zugawa ta hanya mai laushi. J. Physiol. 232, 331-356. [PMC free article] [PubMed]
Bonci A., Malenka RC (1999). Abubuwan mallakar da filasti na synapses a kan kwayoyin halitta da kuma GABAergic a cikin yanki na kwakwalwa. J. Neurosci. 19, 3723-3730. [PubMed]
Borgland SL, Malenka RC, Bonci A. (2004). Maganin cocaine mai tsanani da na yau da kullum suna haifar da rashin ƙarfi na ƙarfin synaptic a cikin tashe-tashen hankulan ƙwayar cuta: ilimin electrophysiological da kuma hali ya dace a ratsan mutum. J. Neurosci. 24, 7482-7490. Doi: 10.1523 / JNEUROSCI.1312-04.2004. [PubMed] [Cross Ref]
Borgland SL, Taha SA, Sarti F., Fields HL, Bonci A. (2006). Orexin A a cikin VTA yana da mahimmanci don haɓaka synptic filastity da haɓaka hali zuwa cocaine. Neuron 49, 589-601. Doi: 10.1016 / j.neuron.2006.01.016. [PubMed] [Cross Ref]
Boudreau AC, Reimers JM, Milovanovic M., Wolf ME (2007). Masu sauraron salula a cikin salula a cikin ƙwayar rat yana kara karuwa a yayin cirewar cocaine amma sunyi aiki bayan kalubalen cocaine a cikin haɗuwa da sauyawar kunnawa na kin furotin da aka haɓaka ta haɗari. J. Neurosci. 27, 10621-10635. Doi: 10.1523 / JNEUROSCI.2163-07.2007. [PMC free article] [PubMed] [Cross Ref]
Boudreau AC, Wolf ME (2005). Hakanan halayyar kwaskwarima ga cocaine yana hade da ƙara yawan adreshin mai karɓa na AMPA a cikin ƙwayar mahaifa.. J. Neurosci. 25, 9144-9151. Doi: 10.1523 / JNEUROSCI.2252-05.2005. [PubMed] [Cross Ref]
Brebner K., Wong TP, Liu L., Liu Y., Campsall P., Gray S., et al. (2005). Tsakanin yana haifar da matsanancin matsanancin matsanancin matsananciyar zuciya da kuma furcin labarun hali. Science 310, 1340-1343. Doi: 10.1126 / kimiyya.1116894. [PubMed] [Cross Ref]
Bredy TW, Sun RA, Kobor MS (2010). Ta yaya burbushin ya taimaka wajen bunkasa cututtuka na psychiatric. Dev. Psychobiol. 52, 331-342. Doi: 10.1002 / dev.20424. [PMC free article] [PubMed] [Cross Ref]
Bredy TW, Wu H., Crego C., Zellhoefer J., Sun RA, Barad M. (2007). Tarihin gyare-gyaren tarihi na kowane mutum BDNF masu haɓaka kwalliya a cikin ƙwayoyin cuta na farko suna haɗuwa da nau'i na tsoro. Koyi. Mem. 14, 268-276. Doi: 10.1101 / lm.500907. [PMC free article] [PubMed] [Cross Ref]
Brown MTC, Bellone C., Mameli M., Labouebe G., Bocklisch C., Balland B., et al. (2010). Rikicin mai karfin AMPA mai ƙwayar cuta ya raguwa ta hanyar daɗaɗɗen motsa jiki na kwayoyin halitta. KUMA KUMA 5: e15870. Doi: 10.1371 / journal.pone.0015870. [PMC free article] [PubMed] [Cross Ref]
Brunzell DH, Ma'adinan YS, Neve RL, Picciotto MR (2009). Mahimmancin haɓaka aikin CREB ya zama wajibi ne don nicotine yanayin da ake so. Neuropsychopharmacology 34, 1993-2001. Doi: 10.1038 / npp.2009.11. [PMC free article] [PubMed] [Cross Ref]
Cadoni C., Pisanu A., Solinas M., Acquas E., Di Chiara G. (2001). Bayanin da ke tattare da kwakwalwa bayan da aka sake bayyanawa zuwa Delta 9-tetrahydrocannabinol da kuma haɗin giciye tare da morphine. Psychopharmacology 158, 259-266. Doi: 10.1007 / s002130100875. [PubMed] [Cross Ref]
Cajal SR (1894). Kyakkyawan tsari na cibiyoyin cibiyoyin. Shaida. R. Soc. London. B Bio. 55, 444-468.
Carlezon WA, Jr., Boundy VA, Haile CN, Lane SB, Kalb RG, Neve RL, et al. (1997). Sensitization zuwa morphine haifar da hanyar canzawa ta hanyar sarrafawa ta hanyar hoto. Science 277, 812-814. Doi: 10.1126 / kimiyya.277.5327.812. [PubMed] [Cross Ref]
Carlezon WA, Jr., Nestler EJ (2002). Matakan da aka haɓaka a GluR1 a cikin tsakiyarbrain: wani abin da zai haifar da hankali ga magungunan zalunci? Trends Neurosci. 25, 610–615. doi: 10.1016/S0166-2236(02)02289-0. [PubMed] [Cross Ref]
Carlezon WA, Jr., Thome J., Olson VG, Lane-Ladd SB, Brodkin ES, Hiroi N., et al. (1998). Dokar cinikin cocaine ta hanyar CREB. Science 282, 2272-2275. Doi: 10.1126 / kimiyya.282.5397.2272. [PubMed] [Cross Ref]
Cha-Molstad H., Keller DM, Yochum GS, Impey S., Goodman RH (2004). Takaddun ƙwayoyin salula na sakon ƙididdigar CREB zuwa sashi mai amsawa ta hanyar CAMP-amsa. Shaida. Natl. Acad. Sci. Amurka. 101, 13572-13577. Doi: 10.1073 / pnas.0405587101. [PMC free article] [PubMed] [Cross Ref]
Chao J., Nestler EJ (2004). Magungunan kwayoyin halitta na ƙwayar maganin miyagun ƙwayoyi. Annu. Rev. Med. 55, 113-132. Doi: 10.1146 / annurev.med.55.091902.103730. [PubMed] [Cross Ref]
Chen BT, Bowers MS, Martin M., Hopf FW, Guillory AM, Carelli RM, et al. (2008). Cocaine amma ba kyakkyawan sakamako na gwamnati ba ne ko jinsin cocaine mai wucewa yana samar da LTP mai karfi a cikin VTA. Neuron 59, 288-297. Doi: 10.1016 / j.neuron.2008.05.024. [PMC free article] [PubMed] [Cross Ref]
Choe ES, Chung KT, Mao L., Wang JQ (2002). Amphetamine qara phosphorylation na alamar siginar siginar-ƙaddamar da sakonni da takardun shaida a cikin rat striatum ta hanyar rukuni na masu karɓa mai cin gashin metabotropic. Neuropsychopharmacology 27, 565–575. doi: 10.1016/S0893-133X(02)00341-X. [PubMed] [Cross Ref]
Choi KH, Whisler K., Graham DL, Kai DW (2006). Rashin raguwa da ƙananan ƙwayoyin cuta a cikin ƙananan ƙwayoyin haɗin gwiwar AMP na haɗin gizon da ke haɓaka ta haɓaka cocaine. Neuroscience 137, 373-383. Doi: 10.1016 / j.neuroscience.2005.10.049. [PubMed] [Cross Ref]
Citri A., Malenka RC (2008). Harshen Synaptic: siffofin da yawa, ayyuka, da kuma hanyoyin. Neuropsychopharmacology 33, 18-41. Doi: 10.1038 / sj.npp.1301559. [PubMed] [Cross Ref]
Colby CR, Whisler K., Steffen C., Nestler EJ, Kai DW (2003). Ƙararren ƙwayoyin sirri na musamman na DeltaFosB yana ƙarfafa haɗin cocaine. J. Neurosci. 23, 2488-2493. [PubMed]
Conrad KL, Tseng KY, Uejima JL, Reimers JM, Heng L.-J., Shaham Y., et al. (2008). Harshen GluR2-rashin masu karbi na AMPA su ne masu haɗaka da haɗin cocaine.. Nature 454, 118-121. Doi: 10.1038 / nature06995. [PMC free article] [PubMed] [Cross Ref]
Cornish JL, Kalivas PW (2000). Glutamate watsa a cikin tsakiya accumbens sake dawowa a cocaine buri. J. Neurosci. 20, RC89. [PubMed]
Crombag HS, Shaham Y. (2002). Sabuntawa na magungunan miyagun ƙwayoyin neman bayanai ta hanyar mahallin bayan an shafe tsawon lokaci a cikin berayen. Behav. Neurosci. 116, 169-173. [PubMed]
Cunningham CL, Noble D. (1992). Amfani da yanayin da ethanol ya haifar da shi a cikin haɓakawa da fifikon wuri mai kyau. Pharmacol. Biochem. Behav. 43, 307-313. [PubMed]
Denu JM (2005). Aikin Sir 2 na protein deacetylases. Curr. Koma. Chem. Biol. 9, 431-440. Doi: 10.1016 / j.cbpa.2005.08.010. [PubMed] [Cross Ref]
Deroche-Gamonet V., Belin D., Piazza PV (2004). Shaidun shaida game da dabi'a-kamar hali a cikin bera. Science 305, 1014-1017. Doi: 10.1126 / kimiyya.1099020. [PubMed] [Cross Ref]
Dewit H., Stewart J. (1981). Amincewa da cocaine-ƙarfafa amsawa a cikin bera. Psychopharmacology 75, 134-143. [PubMed]
Di Chiara G., Imperato A. (1988). Magungunan ƙwayoyi da mutane ke ciwo suna da karuwa da yawa a cikin tsarin mesolimbic na ratsan motsi.. Shaida. Natl. Acad. Sci. Amurka. 85, 5274-5278. [PMC free article] [PubMed]
Dobi A., Seabold GK, Christensen CH, Bock R., Alvarez VA (2011). Rashin haɗi na cocaine a cikin ƙananan ƙwayoyin halitta shine ƙwayoyin halitta kuma yana tasowa ba tare da janyewar lokaci ba. J. Neurosci. 31, 1895-1904. Doi: 10.1523 / JNEUROSCI.5375-10.2011. [PMC free article] [PubMed] [Cross Ref]
Dong Y., Green T., Saal D., Marie H., Neve R., Nestler EJ, et al. (2006). CREB yana ƙaddamar da hanzari na ƙwayoyin wucin gadi. Nat. Neurosci. 9, 475-477. Doi: 10.1074 / jbc.M706578200. [PubMed] [Cross Ref]
Dong Y., Saal D., Thomas M., Faust R., Bonci A., Robinson T., et al. (2004). Cocaine ya haifar da rashin ƙarfi na ƙarfin synaptic a cikin jerin kwayoyin dopamine: hali ya dace a GluRA (- / -) ƙuda. Shaida. Natl. Acad. Sci. Amurka. 101, 14282-14287. Doi: 10.1073 / pnas.0401553101. [PMC free article] [PubMed] [Cross Ref]
Dumont EC, Mark GP, Mader S., Williams JT (2005). Gudanar da kai na inganta ingantaccen maganin synaptic a cikin gado na gado daga cikin shinge. Nat. Neurosci. 8, 413-414. Doi: 10.1038 / nn1414. [PubMed] [Cross Ref]
Engblom D., Bilbao A., Sanchis-Segura C., Dahan L., Perreau-Lenz S., Balland B., et al. (2008). Glutamate masu karɓa a kan kwayoyin dopamine suna kula da ci gaba da neman cocaine. Neuron 59, 497-508. Doi: 10.1016 / j.neuron.2008.07.010. [PubMed] [Cross Ref]
Erb S., Shaham Y., Stewart J. (1996). Ƙwarewa ya sake shigar da halayen hawan cocaine bayan an shafe tsawon lokaci da kuma wani lokaci ba tare da magani ba. Psychopharmacology 128, 408-412. [PubMed]
Faleiro LJ, Jones S., Kauer JA (2004). Hanyoyin sassauci na magungunan ƙwayoyin cuta a kan ƙananan ƙwayoyin cuta na dopamine a cikin ƙananan kwakwalwa don amsawa ga injin amphetamine mai tsanani. Neuropsychopharmacology 29, 2115-2125. Doi: 10.1038 / sj.npp.1300495. [PubMed] [Cross Ref]
Mai daraja KR, Daresan V., Sadri-Vakili G., Schmidt HD, Mierke DF, Cha J.-HJ, et al. (2008). Harkokin fatauci na fataucin GluR2-dauke da masu karɓa na AMPA a cikin mahaifa accumbens suna taka muhimmiyar rawa wajen sake dawowa da neman cocaine. J. Neurosci. 28, 11061-11070. Doi: 10.1523 / JNEUROSCI.1221-08.2008. [PMC free article] [PubMed] [Cross Ref]
Fasano S., Pittenger C., Brambilla R. (2009). Hanawa na aikin CREB a cikin ɓangaren dorsal na striatum mai halayyar halin halayen halayen maganin magunguna. Gabar. Behav. Neurosci. 3:29. Doi: 10.3389 / neuro.08.029.2009. [PMC free article] [PubMed] [Cross Ref]
Ferrario CR, Li X., Wang X., Reimers JM, Uejima JL, Wolf ME (2010). Matsayin da mai karɓar suturar keyi ya jawowa cikin haɓakar locomotor zuwa cocaine. Neuropsychopharmacology 35, 818-833. Doi: 10.1038 / npp.2009.190. [PMC free article] [PubMed] [Cross Ref]
Fu Y., Pollandt S., Liu J., Krishnan B., Genzer K., Orozco-Cabal L., et al. (2007). Dogon lokaci mai yaduwa (LTP) a tsakiyar amygdala (CeA) yana inganta bayan an cire janyewar lokaci daga cocaine na kullum kuma yana buƙatar masu karɓar CRF1. J. Neurophysiol. 97, 937-941. Doi: 10.1152 / jn.00349.2006. [PubMed] [Cross Ref]
Gao M., Jin Y., Yang K., Zhang D., Lukas RJ, Wu J. (2010). Hanyoyin da ke tattare da filastar synaptic mai amfani da nicotine a cikin kwayoyin halitta na kwayoyin halitta a cikin ƙananan ƙananan ƙwayoyin cuta. J. Neurosci. 30, 13814-13825. Doi: 10.1523 / JNEUROSCI.1943-10.2010. [PMC free article] [PubMed] [Cross Ref]
Geisler S., Hikimar RA (2008). Ayyukan aiki na fassarar ƙuƙwalwa a cikin ƙananan yanki. Rev. Neurosci. 19, 227-244. [PMC free article] [PubMed]
Goldman D., Oroszi G., Ducci F. (2005). Kwayoyin jita-jita: kwance jini. Nat. Rev. Genet. 6, 521-532. Doi: 10.1038 / nrg1635. [PubMed] [Cross Ref]
Good CH, Lupica CR (2010). Mahimmanci na musamman na AMPA mai karɓa da ƙaddarar ƙwayar cuta ta synaptic a tsakiyar ƙwayar kwayoyin kwayoyi ta kwayoyi masu amfani da kwayoyi.. J. Neurosci. 30, 7900-7909. Doi: 10.1523 / JNEUROSCI.1507-10.2010. [PMC free article] [PubMed] [Cross Ref]
Graham DL, Edwards S., Bachtell RK, Dileone RJ, Rios M., DW (2007). Aiki na Dynamic BDNF a tsakiya da ke haɓaka da hawan cocaine yana ƙaruwa da kula da kai da kuma sake dawowa. Nat. Neurosci. 10, 1029-1037. Doi: 10.1038 / nn1929. [PubMed] [Cross Ref]
Graybiel AM, Moratalla R., Robertson HA (1990). Amphetamine da Cocaine sunyi amfani da ƙwayoyi na musamman na gwargwadon c-fos a cikin ƙananan matrix-matrix da kuma subdivisions limbic na striatum. Shaida. Natl. Acad. Sci. Amurka. 87, 6912-6916. [PMC free article] [PubMed]
Green TA, Alibhai IN, Roybal CN, Winstanley CA, Theobald DEH, Birnbaum SG, et al. (2010). Amfanin muhalli yana haifar da samfurin kwaikwayon kwaikwayon da ake amfani da shi ta hanyar adadin adonosine monophosphate mai ƙananan yanayi (CREB) a cikin tsakiya na accumbens. Biol. Siyayi 67, 28-35. Doi: 10.1016 / j.biopsych.2009.06.022. [PMC free article] [PubMed] [Cross Ref]
Grillner P., Mercuri NB (2002). Abubuwan da ke cikin kwayoyin halitta da kuma bayanai na synaptic da ke tsara aikin yin amfani da kamfanonin sarrafa kwayoyin dopamine. Behav. Brain Res. 130, 149–169. doi: 10.1016/S0166-4328(01)00418-1. [PubMed] [Cross Ref]
Grimm JW, Lu L., Hayashi T., Hope BT, Su T.-P., Shaham Y. (2003). Tsaran lokaci yana ƙaruwa a cikin ƙwaƙwalwar ƙwayar ƙwayar ƙwayoyin matsala neurotrophic a cikin tsarin tsarin kwayoyin mesolimbic bayan janye daga cocaine: abubuwan da zasu haifar da haɗin cocaine craving. J. Neurosci. 23, 742-747. [PubMed]
Guan Y.-Z., Ye J.-H. (2010). Tsarin Ethanol na dogon lokaci na farfadowa na GABAergic synapses a cikin ɓangaren ƙananan kwakwalwa wanda ya shafi masu karɓan mu-opioid. Neuropsychopharmacology 35, 1841-1849. Doi: 10.1038 / npp.2010.51. [PMC free article] [PubMed] [Cross Ref]
Hong Kong, Chen CHH, Liu THH, Chang H.-F., Liou J.-C. (2012). Maganin kinin kinase mzeta wajibi ne don halayyar synaptic mai kwakwalwa a cocaine a cikin yanki. Biol. Siyayi 71, 706-713. Doi: 10.1016 / j.biopsych.2011.10.031. [PubMed] [Cross Ref]
Hollander JA, Im H.-I., Amelio AL, Kocerha J., Bali P., Lu Q., et al. (2010). Ma'aikatar microRNA ta kwakwalwa tana amfani da maganin cocaine ta hanyar alamar CREB. Nature 466, 197-202. Doi: 10.1038 / nature09202. [PMC free article] [PubMed] [Cross Ref]
Fata B., Kosofsky B., Hyman SE, Nestler EJ (1992). Umurnin samarda asalin jigilar farko da kuma AP-1 da ke ɗaure a cikin ƙwayar rat yana karawa da cocaine na yau da kullum. Shaida. Natl. Acad. Sci. Amurka. 89, 5764-5768. [PMC free article] [PubMed]
Fata BT, Ya ba shi, Kelz MB, Kai DW, Iadarola MJ, Nakabeppu Y., et al. (1994). Ƙaddamar da wani nau'in AP-1 mai dindindin wanda ya hada da sunadaran Fos-kamar sunadaran a kwakwalwa ta hanyar cocaine na yau da kullum da sauran jiyya na yau da kullum. Neuron 13, 1235–1244. doi: 10.1016/0896-6273(94)90061-2. [PubMed] [Cross Ref]
Horger BA, Iyasere CA, Berhow MT, Messer CJ, Nestler EJ, Taylor JR (1999). Haɓaka aikin aiki na locomotor da sakamako mai ladabi ga cocaine ta hanyar ƙwararren neurotrophic. J. Neurosci. 19, 4110-4122. [PubMed]
Huang YH, Lin Y., Mu P., Lee BR, Brown TE, Wayman G., et al. (2009). A cikin vivo cocaine kwarewa haifar da shiru synapses. Neuron 63, 40-47. Doi: 10.1016 / j.neuron.2009.06.007. [PMC free article] [PubMed] [Cross Ref]
Hyman SE (2005). Addiction: cututtuka na ilmantarwa da ƙwaƙwalwa. Am. J. Siyayi 162, 1414-1422. Doi: 10.1176 / appi.ajp.162.8.1414. [PubMed] [Cross Ref]
Hyman SE, Malenka RC, Nestler EJ (2006). Hanyoyi masu mahimmanci na jaraba: nauyin ilmantarwa da ƙwarewa game da sakamako. Annu. Rev. Neurosci. 29, 565-598. Doi: 10.1146 / annurev.neuro.29.051605.113009. [PubMed] [Cross Ref]
Im H.-I., Hollander JA, Bali P., Kenny PJ (2010). MeCP2 sarrafa BDNF magana da haɗin cocaine ta hanyar hulɗar gidaostatic tare da microRNA-212. Nat. Neurosci. 13, 1120-1127. Doi: 10.1038 / nn.2615. [PMC free article] [PubMed] [Cross Ref]
Isaac JT, Nicoll RA, Malenka RC (1995). Tabbatar da shi don tsararren murya: abubuwan da ake nufi don bayyana LTP. Neuron 15, 427–434. doi: 10.1016/0896-6273(95)90046-2. [PubMed] [Cross Ref]
Isaac JTR, Ashby MC, McBain CJ (2007). Rawar da GluR2 ke takawa a aikin AMP receptor da synaptic plasticity. Neuron 54, 859-871. Doi: 10.1016 / j.neuron.2007.06.001. [PubMed] [Cross Ref]
Itzhak Y., Martin JL (1999). Hanyoyin maganin cocaine, nicotine, dizocipline da barasa a kan aikin haɗin gwiwar ƙwayar ƙwayar cuta: haɗin gwiwar hawan cocaine - abin da ke tattare da kwayar cutar shan giya ya haɗu da rashin daidaituwa game da tasirin shuke-shuke na dopamine.. Brain Res. 818, 204–211. doi: 10.1016/S0006-8993(98)01260-8. [PubMed] [Cross Ref]
Jeanes ZM, Buske TR, Morrisett RA (2011). A cikin vivo yayinda rikice-rikice na éthanol na yau da kullum ya sake juyayi da mahimmanci na synptic filastik a cikin tsakiya na accumbens. J. Pharmacol. Exp. Ther. 336, 155-164. Doi: 10.1124 / jpet.110.171009. [PMC free article] [PubMed] [Cross Ref]
Jing L., Luo J., Zhang M., Qin W.-J., Li YLL, Liu Q., et al. (2011). Sakamakon tarihi na masu binciken histone deacetylase a kan halayyar halayyar mutum zuwa ga wani nau'i na morphine wanda ke nunawa a cikin mice. Neurosci. Lett. 494, 169-173. Doi: 10.1016 / j.neulet.2011.03.005. [PubMed] [Cross Ref]
Kalivas PW (2009). Maganar gida mai amfani da gurbataccen gida na jaraba. Nat. Rev. Neurosci. 10, 561-572. Doi: 10.1038 / nrn2515. [PubMed] [Cross Ref]
Kalivas PW, Duffy P. (1987). Sensitization don sake yin allurar morphine a cikin bera - yiwuwar shiga cikin A10 dopamine neurons. J. Pharmacol. Exp. Ther. 241, 204-212. [PubMed]
Kalivas PW, Lalumiere RT, Knackstedt L., Shen H. (2009). Glutamate watsa a cikin buri. Neuropharmacology 56Suppl. 1, 169-173. Doi: 10.1016 / j.neuropharm.2008.07.011. [PMC free article] [PubMed] [Cross Ref]
Kalivas PW, O'Brien C. (2008). Magungunan ƙwayoyi na Drug a matsayin maganin maganin neuroplasticity. Neuropsychopharmacology 33, 166-180. Doi: 10.1038 / sj.npp.1301564. [PubMed] [Cross Ref]
Kalivas PW, Volkow N., Sani J. (2005). Dalili mai sauki ba tare da dalili ba a cikin jaraba: maganin da ke cikin gaba-gaba-daɗaɗɗen yaduwa. Neuron 45, 647-650. Doi: 10.1016 / j.neuron.2005.02.005. [PubMed] [Cross Ref]
Kandel D. (1975). Hanyoyin shiga a cikin yarinya a cikin amfani da miyagun ƙwayoyi. Science 190, 912-914. Doi: 10.1126 / kimiyya.1188374. [PubMed] [Cross Ref]
Kandel DB, Yamaguchi K., Chen K. (1992). Matakan ci gaba a cikin shigar da ƙwayoyi tun daga samartaka har zuwa girma - ƙarin shaida ga ka'idar ƙofar. J. Stud. Barasa 53, 447-457. [PubMed]
Kandel ER (2001). Kwayoyin kwayoyin halitta na ƙwaƙwalwar ajiya: tattaunawa tsakanin kwayoyin halitta da synapses. Science 294, 1030-1038. Doi: 10.1126 / kimiyya.1067020. [PubMed] [Cross Ref]
Kano T., Suzuki Y., Shibuya M., Kiuchi K., Hagiwara M. (1995). Anyi amfani da CREB phosphorylation da C-Fos maganin maganin Cocaine a cikin tsarin Parkinsonism.. Neuroreport 6, 2197-2200. [PubMed]
Kao J.-H., Huang EY-K., Tao P.-L. (2011). Rashin NR2B na mai karɓa na NMDA a ƙananan ƙwayoyin cuta yana cikin sakamakon morphine sakamakon sakamako daga siRNA. Drug Barasa dogara. 118, 366-374. Doi: 10.1016 / j.drugalcdep.2011.04.019. [PubMed] [Cross Ref]
Kasanetz F., Deroche-Gamonet V., Berson N., Balado E., Lafourcade M., Manzoni O., et al. (2010). Tsarin cigaba ga jaraba yana haɗuwa da rashin ci gaba a cikin ladaran synaptic. Science 328, 1709-1712. Doi: 10.1126 / kimiyya.1187801. [PubMed] [Cross Ref]
Kauer JA, Malenka RC (2007). Harshen Synaptic da kuma jaraba. Nat. Rev. Neurosci. 8, 844-858. Doi: 10.1038 / nrn2234. [PubMed] [Cross Ref]
Kelley AE (2004). Gudanar da kwakwalwa na motsa jiki na motsa jiki: rawar da ke tattare da rikici da ilmantarwa. Neurosci. Biobehav. Rev. 27, 765-776. Doi: 10.1016 / j.neubiorev.2003.11.015. [PubMed] [Cross Ref]
Kelz MB, Chen J., Carlezon WA, Jr., Whisler K., Gilden L., Beckmann AM, et al. (1999). Magana game da batun sakonnin deltaFosB a cikin kwakwalwa yana kula da hankali ga cocaine. Nature 401, 272-276. Doi: 10.1038 / 45790. [PubMed] [Cross Ref]
Kendler KS, Myers J., Prescott CA (2007). Musamman game da kwayoyin halitta da abubuwan haɗarin muhalli don alamun cututtuka na cannabis, cocaine, barasa, maganin kafeyin, da kuma dogara ga nicotine. Arch. Gen. Psychiatry 64, 1313-1320. Doi: 10.1001 / archpsyc.64.11.1313. [PubMed] [Cross Ref]
Konradi C., Cole RL, Heckers S., Hyman SE (1994). Amphetamine ya samar da jigilar kalma a cikin rat striatum ta hanyar takardun sakonni CREB. J. Neurosci. 14, 5623-5634. [PubMed]
Kourrich S., Rothwell PE, Klug JR, Thomas MJ (2007). Kwarewar Cocaine yana sarrafa ikon haɗin gwiwar synaptic a cikin ƙananan ƙwayoyin. J. Neurosci. 27, 7921-7928. Doi: 10.1523 / JNEUROSCI.1859-07.2007. [PubMed] [Cross Ref]
Kouzarides T. (2007). Tsarin gyaran Chromatin da aikin su. cell 128, 693-705. Doi: 10.1016 / j.cell.2007.02.005. [PubMed] [Cross Ref]
Kumar A., Choi K.-H., Renthal W., Tsankova NM, Theobald DEH, Truong H.-T., et al. (2005). Tsarin gyaran Chromatin shine wata hanya mai mahimmanci da ke haifar da cocaine - haɓakawa a cikin striatum. Neuron 48, 303-314. Doi: 10.1016 / j.neuron.2005.09.023. [PubMed] [Cross Ref]
Lalumiere RT, Kalivas PW (2008). Glutamate saki a cikin tsakiya accumbens core ya zama dole don heroin neman. J. Neurosci. 28, 3170-3177. Doi: 10.1523 / JNEUROSCI.5129-07.2008. [PubMed] [Cross Ref]
Lammel S., Ion DI, Roeper J., Malenka RC (2011). Dangantaka na musamman na dopamine neuron synapses ta hanyar juyayi da ladabi. Neuron 70, 855-862. Doi: 10.1016 / j.neuron.2011.03.025. [PMC free article] [PubMed] [Cross Ref]
Laplant Q., Vialou V., Covington HE, 3rd., Dumitriu D., Feng J., Warren BL, et al. (2010). Dnmt3a ya tsara dabi'un motsa jiki da kuma lakabi a cikin mahaifa acumbens. Nat. Neurosci. 13, 1137-1143. Doi: 10.1038 / nn.2619. [PMC free article] [PubMed] [Cross Ref]
Larson EB, Graham DL, Arzaga RR, Buzin N., Webb J., Green TA, et al. (2011). Cikakken CREB a cikin ƙwayar da ake ciki yana kara ƙarfafa hawan cocaine a cikin yin amfani da haruffa. J. Neurosci. 31, 16447-16457. Doi: 10.1523 / JNEUROSCI.3070-11.2011. [PMC free article] [PubMed] [Cross Ref]
Lattal KM, Barrett RM, Wood MA (2007). Bayyanar tsari ko ƙaddamarwa na maƙasudin tarihi na histone deacetylase yana taimakawa tsoron ƙyama. Behav. Neurosci. 121, 1125-1131. Doi: 10.1037 / 0735-7044.121.5.1125. [PubMed] [Cross Ref]
Le Moal M., Simon H. (1991). Cibiyar maganin maganin maganin Mesocorticolimbic: aikin aiki da ka'ida. Physiol. Rev. 71, 155-234. [PubMed]
Letchworth SR, Nader MA, Smith HR, Friedman DP, Porrino LJ (2001). Canje-canje na canje-canje a cikin tsarkewar kwayoyin halitta a sakamakon gwanin cocaine a rhesus birai. J. Neurosci. 21, 2799-2807. [PubMed]
Levine A., Huang Y., Drisaldi B., Griffin EA, Jr., Pollak DD, Xu S., et al. (2011). Tsarin kwayoyin halitta don ƙwayar magungunan ƙwayar cuta: cututtukan epigenetic da aka fara ta hanyar ƙwayoyin firam na nicotine ta hanyar cocaine. Sci. Transl. Mad. 3, 107ra109. Doi: 10.1126 / scitranslmed.3003062. [PubMed] [Cross Ref]
Levine AA, Guan Z., Barco A., Xu S., Kandel ER, Schwartz JH (2005). Kwayar haɗin CREB da ke haɗakar hawan cocaine ta hanyar binciken acetylating a fosB na kasuwa a cikin siginar motsi. Shaida. Natl. Acad. Sci. Amurka. 102, 19186-19191. Doi: 10.1073 / pnas.0509735102. [PMC free article] [PubMed] [Cross Ref]
Liu Q.-S., Pu L., Poo M.-M. (2005). Maganin cocaine mai maimaitawa a vivo Yana inganta shigarwa na LTP a cikin kwakwalwa ta tsakiya. Nature 437, 1027-1031. Doi: 10.1038 / nature04050. [PMC free article] [PubMed] [Cross Ref]
Loidl P. (1994). Tarihin acetylation: gaskiya da tambayoyi. Chromosoma 103, 441-449. [PubMed]
Luger K., Mader AW, Richmond RK, Sargent DF, Richmond TJ (1997). Tsarin gine-gine na ƙwayar maɓallin halitta a 2.8 A ƙuduri. Nature 389, 251-260. Doi: 10.1016 / j.bbagrm.2009.11.018. [PubMed] [Cross Ref]
Luscher C., Malenka RC (2011). Hanyoyin launin fata na maganin ƙwayar cuta ta hanyar ƙwayar cuta ta hanyar ƙwayar cuta: daga kwayoyin sun canza zuwa gyaran gyare-gyare. Neuron 69, 650-663. Doi: 10.1016 / j.neuron.2011.01.017. [PubMed] [Cross Ref]
Luu P., Malenka RC (2008). Gwaran lokaci na tsoma baki a cikin ƙananan ƙwayoyin jiki na kwayoyin dopamine yana buƙatar PKC. J. Neurophysiol. 100, 533-538. Doi: 10.1152 / jn.01384.2007. [PMC free article] [PubMed] [Cross Ref]
Madsen HB, Navaratnarajah S., Farrugia J., Djouma E., Ehrlich M., Mantamadiotis T., et al. (2012). CREB1 da CREB-daurin haɗin furotin a cikin matsakaicin matsakaici na masu amfani da ƙananan igiyoyi suna tsara halayyar hali ga psychostimulants. Psychopharmacology 219, 699–713. doi: 10.1007/s00213-011-2406-1. [PubMed] [Cross Ref]
Malenka RC, Bear MF (2004). LTP da LTD: kunya daga dukiya. Neuron 44, 5-21. Doi: 10.1016 / j.nlm.2007.11.004. [PubMed] [Cross Ref]
Malvaez M., Mhillaj E., Matheos DP, Palmery M., Wood MA (2011). Kwanan CBP a cikin ƙananan ƙwayoyin cuta yana ƙayyade tarihin maganin maganin cocaine kuma yana da mahimmanci ga halin halayyar haɗin cocaine. J. Neurosci. 31, 16941-16948. Doi: 10.1523 / JNEUROSCI.2747-11.2011. [PMC free article] [PubMed] [Cross Ref]
Malvaez M., Sanchis-Segura C., Vo D., Lattal KM, Wood MA (2010). Hanyoyin gyara na chromatin yana taimakawa wajen ƙaddamar da wuri mai mahimmanci na wuri mai sanyaya. Biol. Siyayi 67, 36-43. Doi: 10.1016 / j.biopsych.2009.07.032. [PMC free article] [PubMed] [Cross Ref]
Mamel M., Balland B., Lujan R., Luscher C. (2007). Hanyar kira da sauri da GluR2 don mGluR-LTD a cikin yanki na kwakwalwa. Science 317, 530-533. Doi: 10.1126 / kimiyya.1142365. [PubMed] [Cross Ref]
Mameli M., Bellone C., Kawa MTC, Luscher C. (2011). Cocaine ya juya dokokin da ake amfani da su na synaptic na yaduwa a cikin sassan jiki. Nat. Neurosci. 14, 414-416. Doi: 10.1038 / nn.2763. [PubMed] [Cross Ref]
Mamel M., Halbe B., Creton C., Engblom D., Parkitna JR, Spanagel R., et al. (2009). Hanyoyin haɗi na synaptic cocaine-haɓakawa: jurewa a cikin VTA yana da haɓakawa a cikin NAc. Nat. Neurosci. 12, 1036-1041. Doi: 10.1038 / nn.2367. [PubMed] [Cross Ref]
Mao D., Gallagher K., McGehee DS (2011). Nicotine yiwuwar haɗakarwa ta hanyar intitatory zuwa ƙananan ƙananan ƙananan hanyoyi. J. Neurosci. 31, 6710-6720. Doi: 10.1523 / JNEUROSCI.5671-10.2011. [PMC free article] [PubMed] [Cross Ref]
Martin M., Chen BT, Hopf FW, Bowers MS, Bonci A. (2006). Cibiyar kula da kankara ta Cocaine ta kawar da LTD a tsakiya na ƙananan mahaifa. Nat. Neurosci. 9, 868-869. Doi: 10.1038 / nn1713. [PubMed] [Cross Ref]
Mayr B., Montminy M. (2001). Dokar rubutun ta hanyar factor factor dependent phosphorylation CREB. Nat. Rev. Mol. Cell Biol. 2, 599-609. Doi: 10.1038 / 35085068. [PubMed] [Cross Ref]
Maze I., Covington HE, 3rd., Dietz DM, Laplant Q., Renthal W., Russo SJ, et al. (2010). Muhimmin muhimmancin tarihin methyltransferase G9a a cikin nauyin halayyar hawan cocaine. Science 327, 213-216. Doi: 10.1126 / kimiyya.1179438. [PMC free article] [PubMed] [Cross Ref]
Maze I., Feng J., Wilkinson MB, Sun H., Shen L., Nestler EJ (2011). Cocaine yana da ikon sarrafa tsarin heterochromatin da kuma sakewa mai mahimmanci a tsakiya acumbens. Shaida. Natl. Acad. Sci. Amurka. 108, 3035-3040. Doi: 10.1073 / pnas.1015483108. [PMC free article] [PubMed] [Cross Ref]
Maze I., Nestler EJ (2011). Tsarin asali na jaraba. Ann. NY Acad. Sci. 1216, 99-113. Doi: 10.1111 / j.1749-6632.2010.05893.x. [PMC free article] [PubMed] [Cross Ref]
McClung CA, Nestler EJ (2003). Ƙaddamar da ladabi da ladabi ta hanyar CREB da DeltaFosB. Nat. Neurosci. 6, 1208-1215. Doi: 10.1038 / nn1143. [PubMed] [Cross Ref]
McCutcheon JE, Wang X., Tseng KY, Wolf ME, Marinelli M. (2011). Masu karbaccen ma'auni na AMPA sun kasance a cikin mahalarta accnaral synapses bayan da aka janye tsawon lokaci daga gine-ginen ciwon cocaine amma ba gwaji ba ne.. J. Neurosci. 31, 5737-5743. Doi: 10.1523 / JNEUROSCI.0350-11.2011. [PMC free article] [PubMed] [Cross Ref]
McDaid J., Graham MP, Napier TC (2006). Hanyoyin da aka samu daga Methamphetamine daban-daban ya canza pCREB da DeltaFosB a cikin dukkanin launi na kwakwalwa na kwakwalwa. Mol. Pharmacol. 70, 2064-2074. Doi: 10.1124 / mol.106.023051. [PubMed] [Cross Ref]
McFarland K., Lapish CC, Kalivas PW (2003). Kaddamar da yaduwar launin fata a cikin tsakiya na tsakiya ya haifar da maganin cocaine-induced reinstationment of behavioral-behaving behavioral. J. Neurosci. 23, 3531-3537. [PubMed]
McPherson CS, Lawrence AJ (2007). Hanyoyin sakonnin nukiliya CREB: shiga cikin jaraba, ƙarancin samfurori da kuma sa ido. Curr Neuropharm 5, 202-212. Doi: 10.2174 / 157015907781695937. [PMC free article] [PubMed] [Cross Ref]
McPherson CS, Mantamadiotis T., Tan S.-S., Lawrence AJ (2010). Lalacewar CREB1 daga gidan talabijin na dorsal din yana rage dabi'un halayen hawan cocaine. Cereb. Cortex 20, 941-952. Doi: 10.1093 / cercor / bhp159. [PubMed] [Cross Ref]
McQuown SC, Wood MA (2010). Epigenetic dokoki a cikin wani abu amfani da cuta. Curr. Abun mahimmanci Rep. 12, 145–153. doi: 10.1007/s11920-010-0099-5. [PMC free article] [PubMed] [Cross Ref]
Meil WM, Dubi RE (1996). Anyi kwaskwarima ta dawo da amsawa bayan cirewa mai tsawo daga cocaine mai gudanarwa a cikin berayen: samfurin dabba na koma baya. Behav. Pharmacol. 7, 754-763. [PubMed]
Melis M., Camarini R., Ungless MA, Bonci A. (2002). Damawa na har abada na Gassaragic synapses a cikin kwayoyin kwayoyi bayan daya a vivo ethanol watsawa. J. Neurosci. 22, 2074-2082. [PubMed]
Mitchell PJ, Tjian R. (1989). Tsarin littattafai a cikin kwayoyin halittu ta kwayoyin halitta ta musamman ta DNA. Science 245, 371-378. Doi: 10.1126 / kimiyya.2667136. [PubMed] [Cross Ref]
Morgan JI, Curran T. (1995). Kwayoyin jima-jimawa: shekaru goma a kan. Trends Neurosci. 18, 66–67. doi: 10.1016/0166-2236(95)80022-T. [PubMed] [Cross Ref]
Moussawi K., Pacchioni A., Moran M., Filalin Olive, Gass JT, Lavin A., et al. (2009). N-Acetylcysteine ya sake juyayi cocaine-induced metaplasticity. Nat. Neurosci. 12, 182-189. Doi: 10.1038 / nn.2250. [PMC free article] [PubMed] [Cross Ref]
Moussawi K., Zhou W., Shen H., Cote CM, Dubi RE, Carr DB, et al. (2011). Rashin juyawar halayen maganin maganin cocaine yana haifar da kariya daga sake dawowa. Shaida. Natl. Acad. Sci. Amurka. 108, 385-390. Doi: 10.1073 / pnas.1011265108. [PMC free article] [PubMed] [Cross Ref]
Mueller D., Stewart J. (2000). Yanayin da aka sanya a cikin cocaine zaɓi: sake dawowa ta hanyar ingancin inganci na cocaine bayan ƙaddarawa. Behav. Brain Res. 115, 39–47. doi: 10.1016/S0166-4328(00)00239-4. [PubMed] [Cross Ref]
Muller DL, Unterwald EM (2005). D1 dopamine receptors tsara deltaFosB shigarwa a rat striatum bayan intermittent morphine mulkin. J. Pharmacol. Exp. Ther. 314, 148-154. Doi: 10.1124 / jpet.105.083410. [PubMed] [Cross Ref]
Myers KM, Davis M. (2002). Binciken da ke tattare da ƙananan ƙaura. Neuron 36, 567–584. doi: 10.1016/S0896-6273(02)01064-4. [PubMed] [Cross Ref]
Nan X., Ng HH, Johnson CA, CD da Laherty, Turner BM, Eisenman RN, et al. (1998). Tsarin rubutun ta hanyar methyl-CpG mai gina jiki mai gina jiki MeCP2 ya ƙunshi hadarin historia deacetylase. Nature 393, 386-389. Doi: 10.1038 / 30764. [PubMed] [Cross Ref]
Nestler EJ (2008). Review. Tsarin sakonnin jaraba: tasirin DeltaFosB. Phil. Trans. R. Soc. London. B Biol. Sci. 363, 3245-3255. Doi: 10.1098 / rstb.2008.0067. [PMC free article] [PubMed] [Cross Ref]
Niehaus JL, Murali M., Kauer JA (2010). Magunguna na cin zarafi da damuwa sun lalata LTP a tashe-tashen hankula a cikin yanki na kwakwalwa. Eur. J. Neurosci. 32, 108-117. Doi: 10.1111 / j.1460-9568.2010.07256.x. [PMC free article] [PubMed] [Cross Ref]
Nugent FS, Penick EC, Kauer JA (2007). Kamfanin Opioids na dogon lokaci na farfadowa na synapses inhibitory. Nature 446, 1086-1090. Doi: 10.1038 / nature05726. [PubMed] [Cross Ref]
Ka ba HE, Fata BT, Kelz MB, Iadarola M., Nestler EJ (1995). Nazarin Pharmacological game da tsari na maganin maganin antigen da ke dauke da kwayoyin FOS ta cocaine a cikin striatum da ƙananan ƙwayoyin cuta.. J. Pharmacol. Exp. Ther. 275, 1671-1680. [PubMed]
Bada HE, Nestler EJ (1996). Sakamakon kwakwalwa da ke dauke da kwayoyin cutar kwakwalwa a cikin kwakwalwa ta hanyar ciwon halayen kullun. Mol. Pharmacol. 49, 636-645. [PubMed]
O'Brien CP (1997). Hanyoyin bincike na likitanci na bincike don maganin. Science 278, 66-70. Doi: 10.1126 / kimiyya.278.5335.66. [PubMed] [Cross Ref]
O'Brien CP, Childress AR, Ehrman R., Robbins SJ (1998). Hanyoyin da suka shafi yanayin maganin miyagun ƙwayoyi: shin zasu iya bayyana tilas? J. Psychopharmacol. 12, 15-22. Doi: 10.1177 / 026988119801200103. [PubMed] [Cross Ref]
Padgett CL, Lalive AL, Tan KR, Terunuma M., Munoz MB, Pangalos MN, et al. (2012). Jin ƙwayar maganin Methamphetamine na GABA (B) mai karɓa a cikin GABA neurons na VTA. Neuron 73, 978-989. Doi: 10.1016 / j.neuron.2011.12.031. [PubMed] [Cross Ref]
Pan B., Hillard CJ, Liu Q.-S. (2008). Endocannabinoid siginar yana yaduwar maganin cocaine-induced inhibitory synaptic plasticity in midbrain dopamine neurons. J. Neurosci. 28, 1385-1397. Doi: 10.1523 / JNEUROSCI.4033-07.2008. [PubMed] [Cross Ref]
Pan B., Zhong P., Sun D., Liu Q.-S. (2011). Ƙararren alamar siginar alama-ƙaddamarwa a cikin ƙananan ƙananan hanyoyi na cocaine-induced synaptic plasticity and effects rewarding. J. Neurosci. 31, 11244-11255. Doi: 10.1523 / JNEUROSCI.1040-11.2011. [PMC free article] [PubMed] [Cross Ref]
Pascoli V., Turiault M., Luscher C. (2012). Rushewar halayyar synaptic da aka yadu da hawan cocaine ya sake dawo da halayyar haɓaka da miyagun kwayoyi. Nature 481, 71-75. Doi: 10.1038 / nature10709. [PubMed] [Cross Ref]
Peakman MC, Colby C., Perrotti LI, Tekumalla P., Carle T., Ulery P., et al. (2003). Madafi, ƙwaƙwalwar ƙwayoyin yanki na musamman na yankin C-Jun a cikin ƙananan ƙwayoyin cuta yana rage yawan hankali ga cocaine. Brain Res. 970, 73–86. doi: 10.1016/S0006-8993(03)02230-3. [PubMed] [Cross Ref]
Pich EM, Pagliusi SR, Tessari M., Talabot-Ayer D., Hooft Van Huijsduijnen R., Chiamulera C. (1997). Magungunan ƙwayoyin maƙalai na yau da kullum don abubuwan da ke cike da nicotine da cocaine. Science 275, 83-86. Doi: 10.1126 / kimiyya.275.5296.83. [PubMed] [Cross Ref]
Ping A., Xi J., Prasad BM, Wang MHH, Kruzich PJ (2008). Kyauta ta tsakiya da kuma gilashi GluR1 dauke da masu karɓa na AMPA a AMPA- da kuma farautar cocaine-primed na halin hawan cocaine-behaving. Brain Res. 1215, 173-182. Doi: 10.1016 / j.brainres.2008.03.088. [PMC free article] [PubMed] [Cross Ref]
Filakas AM, Carlson RR, Neve RL, Konradi C., Nestler EJ, Carlezon WA, Jr. (2001). Sakamakon da aka yi da cocaine da ƙara yawan rashin daidaituwa a gwajin gwagwarmaya da aka yi amfani da shi tare da haɓakar amfanar da ake kira CAMP na haɓakar ƙwayar cuta a cikin tsakiya.. J. Neurosci. 21, 7397-7403. [PubMed]
Porrino LJ, Lyons D., Smith HR, Daunais JB, Nader MA (2004). Cibiyar kankara ta Cocaine tana haifar da wani bangare na ƙungiyoyin limbic, ƙungiyoyi, da kuma masu bincike na sassan jiki. J. Neurosci. 24, 3554-3562. Doi: 10.1523 / JNEUROSCI.5578-03.2004. [PubMed] [Cross Ref]
Pulipparacharuvil S., Renthal W., Hale CF, Taniguchi M., Xiao G., Kumar A., et al. (2008). Cocaine ta tsara MEF2 don sarrafa synaptic da kuma filayen hali. Neuron 59, 621-633. Doi: 10.1016 / j.neuron.2008.06.020. [PMC free article] [PubMed] [Cross Ref]
Muryar W., Kumar A., Xiao G., Wilkinson M., Covington HE, 3rd., Maze I., et al. (2009). Yin nazarin ka'idar tsarin chromatin ta hanyar kwakwalwa yana nuna rawar da za a yi ga sirrin. Neuron 62, 335-348. Doi: 10.1016 / j.neuron.2009.03.026. [PMC free article] [PubMed] [Cross Ref]
Muryar W., Maze I., Krishnan V., Covington HE, 3rd., Xiao G., Kumar A., Russo SJ, et al. (2007). Tarihin 5 ta hanyar tarihi yana sarrafa halayyar halayyar kirkiro don ci gaba da motsa jiki. Neuron 56, 517-529. Doi: 10.1016 / j.neuron.2007.09.032. [PubMed] [Cross Ref]
Renthal W., Nestler EJ (2008). Hanyoyi na asali na maganin ƙwayoyi. Trends Mol. Mad. 14, 341-350. Doi: 10.1016 / j.molmed.2008.06.004. [PMC free article] [PubMed] [Cross Ref]
Rice JC, Allis CD (2001). Histone methylation dangane da histone acetylation: sabon fahimci cikin tsarin epigenetic. Curr. Koma. Cell Biol. 13, 263–273. doi: 10.1016/S0955-0674(00)00208-8. [PubMed] [Cross Ref]
Robinson TE, Jurson PA, Bennett JA, Bentgen KM (1988). Ganowa na yau da kullun na neurotransmission a cikin ventral striatum (ƙananan ƙwayoyin cuta) wanda aka samu ta hanyar ƙwarewa ta farko tare da (+) - amphetamine - nazarin microdialysis a cikin berayen da ke motsawa cikin yardar kaina. Brain Res. 462, 211–222. doi: 10.1016/0006-8993(88)90549-5. [PubMed] [Cross Ref]
Robison AJ, Nestler EJ (2011). Hanyoyin sassaucin ra'ayi da jinsin halittu na jaraba. Nat. Rev. Neurosci. 12, 623-637. Doi: 10.1038 / nrn3111. [PMC free article] [PubMed] [Cross Ref]
Romieu P., Mai watsa shiri L., Gobaille S., Sandner G., Aunis D., Zwiller J. (2008). Abun masu maganin tarihin Tarihin na rage karfin cocaine amma ba sukayi jagoran kansu ba a cikin berayen. J. Neurosci. 28, 9342-9348. Doi: 10.1523 / JNEUROSCI.0379-08.2008. [PubMed] [Cross Ref]
Russo SJ, Wilkinson MB, Mazei-Robison MS, Dietz DM, Maze I., Krishnan V., et al. (2009). Kayan ƙwayar makaman nukiliya B na sa hannu akan ƙwayoyin halittar jiki da kuma cocaine. J. Neurosci. 29, 3529-3537. Doi: 10.1523 / JNEUROSCI.6173-08.2009. [PMC free article] [PubMed] [Cross Ref]
Saal D., Dong Y., Bonci A., Malenka RC (2003). Drugs of abuse and stress jawo wani na kowa synaptic daidaitawa a cikin dopamine neurons. Neuron 37, 577–582. doi: 10.1016/S0896-6273(03)00021-7. [PubMed] [Cross Ref]
Sanchez CJ, Sorg BA (2001). Sakamakon farfado da yanayin da ake dashi ya sake komawa wuri mai dorewa na cocaine. Brain Res. 908, 86–92. doi: 10.1016/S0006-8993(01)02638-5. [PubMed] [Cross Ref]
Sanchis-Segura C., Lopez-Atalaya JP, Barco A. (2009). Zaɓuɓɓuka na zaɓuɓɓuka na ƙididdigar rubutu da nuna hali ga magunguna na zalunci ta hanyar hana tarihi ta tarihi. Neuropsychopharmacology 34, 2642-2654. Doi: 10.1038 / npp.2009.125. [PubMed] [Cross Ref]
Schilstrom B., Yaka R., Argilli E., Suvarna N., Schumann J., Chen BT, et al. (2006). Cocaine yana inganta ƙwayoyin mai karɓar mai karɓa na NMDA a cikin ɓangaren sassan jiki na kwakwalwa ta hanyar tsoma baki na D5 mai kwakwalwa na masu karɓa na NMDA. J. Neurosci. 26, 8549-8558. Doi: 10.1523 / JNEUROSCI.5179-05.2006. [PubMed] [Cross Ref]
Schumann J., Matzner H., Michaeli A., Yaka R. (2009). NR2A / B-dauke da masu karɓar NMDA masu kwakwalwa na synaptic masu kwakwalwa a cikin VTA da kuma cocaine psychoitization sensitization. Neurosci. Lett. 461, 159-162. Doi: 10.1016 / j.neulet.2009.06.002. [PubMed] [Cross Ref]
Shaham Y., Stewart J. (1995). Ƙwarewar sake mayar da hankalin jarrabawa a cikin dabbobin da ba su da magani. Psychopharmacology 119, 334-341. [PubMed]
Shen H., Moussawi K., Zhou W., Toda S., Kalivas PW (2011). Rikicin Heroin yana buƙatar tsawon lokaci mai rikitarwa-kamar nau'in filastik wanda NMDA2b ya ƙunshi masu karɓa. Shaida. Natl. Acad. Sci. Amurka. 108, 19407-19412. Doi: 10.1073 / pnas.1112052108. [PMC free article] [PubMed] [Cross Ref]
Shen H.-W., da S. S., Moussawi K., Bouknight A., Zahm DS, Kalivas PW (2009). Sauya dendritic spine plasticity a cikin cocaine-janye berayen. J. Neurosci. 29, 2876-2884. Doi: 10.1523 / JNEUROSCI.5638-08.2009. [PMC free article] [PubMed] [Cross Ref]
Shepard JD, Bossert JM, Liu SY, Shaham Y. (2004). Magungunan rigakafin rigakafin yohimbine ya sake dawo da samfurin da ake bukata a cikin ƙirar ƙwayar magunguna. Biol. Siyayi 55, 1082-1089. Doi: 10.1016 / j.biopsych.2004.02.032. [PubMed] [Cross Ref]
Shuster L., Yu G., Bates A. (1977). Sensitization zuwa cocaine motsa jiki a cikin mice. Psychopharmacology 52, 185-190. [PubMed]
Jirgin Jirgin JD (2003). Tsarin neurotransmitter na magunguna na farko na tsakiya: rawar da take takawa a hankali ga psychostimulants. Brain Res. Rev. 41, 203–228. doi: 10.1016/S0165-0173(02)00233-3. [PubMed] [Cross Ref]
Stolzenberg DS, Grant PA, Bekiranov S. (2011). Ka'idodin jigilar cututtuka don masana kimiyya. Horm. Behav. 59, 407-416. Doi: 10.1016 / j.yhbeh.2010.10.007. [PMC free article] [PubMed] [Cross Ref]
Strahl BD, Allis CD (2000). Harshen covalent histone gyara. Nature 403, 41-45. Doi: 10.1038 / 47412. [PubMed] [Cross Ref]
Cuban GD, Klanker M., De Ridder B., Bowers MS, Joosten RN, Feenstra MG, et al. (2008). Ayyukan al'ajabi na sakamako suna ƙarfafa ƙarfin synaptic a kan kwayoyin tsakiya na tsakiya. Science 321, 1690-1692. Doi: 10.1126 / kimiyya.1160873. [PMC free article] [PubMed] [Cross Ref]
Sun J., Wang L., Jiang B., Hui B., Lv Z., Ma L. (2008). Hanyoyin butyrate na sodium, wani mai hanawa na histone deacetylase, a kan cocaine- da kuma sucrose-kula da kai a cikin ratsi. Neurosci. Lett. 441, 72-76. Doi: 10.1016 / j.neulet.2008.05.010. [PubMed] [Cross Ref]
Tan KR, Brown M., Labouebe G., Yvon C., Creton C., Fritschy J.-M., et al. (2010). Ƙananan kwakwalwa don abubuwan da ake ci na nishaɗi na benzodiazepines. Nature 463, 769-774. Doi: 10.1038 / nature08758. [PMC free article] [PubMed] [Cross Ref]
Taniguchi M., Carreira MB, Smith LN, Zirlin BC, Neve RL, Cowan CW (2012). Tarihin na 5 na Histone ya ƙayyade ladabin cocaine ta hanyar shigar da makaman nukiliya da aka haifa. Neuron 73, 108-120. Doi: 10.1016 / j.neuron.2011.10.032. [PMC free article] [PubMed] [Cross Ref]
Taverna SD, Li H., Ruthenburg AJ, Allis CD, Kayan DJ (2007). Yaya tsarin haɗin kaya-kullin zai fassara fassarar tarihi: darussan daga kwararrun aljihun sana'a. Nat. Struct. Mol. Biol. 14, 1025-1040. Doi: 10.1038 / nsmb1338. [PubMed] [Cross Ref]
Thomas MJ, Beurrier C., Bonci A., Malenka RC (2001). Matsayi na tsawon lokaci a cikin mahaifa:. Nat. Neurosci. 4, 1217-1223. Doi: 10.1038 / nn757. [PubMed] [Cross Ref]
Thomas MJ, Kalivas PW, Shaham Y. (2008). Neuroplasticity a cikin mesolimbic dopamine tsarin da cocaine buri. Br. J. Pharmacol. 154, 327-342. Doi: 10.1038 / bjp.2008.77. [PMC free article] [PubMed] [Cross Ref]
Tiffany ST, Drobes DJ (1990). Hoto da shan taba yana buƙatar: da magudi na abun ciki mai ban sha'awa. Rikicin. Behav. 15, 531-539. [PubMed]
Tzschentke TM (1998). Gwargwadon sakamako tare da yanayin da aka fi so a yanayin da ake ciki: cikakken nazari game da ciwon kwayoyi, ci gaba da cigaba da sababbin al'amura. Prog. Neurobiol. 56, 613–672. doi: 10.1016/S0301-0082(98)00060-4. [PubMed] [Cross Ref]
M, MA, Whistler JL, Malenka RC, Bonci A. (2001). Kwancen cocaine guda daya a vivo yana haifar da tsayin daka na tsawon lokaci a cikin kwayoyin dopamine. Nature 411, 583-587. Doi: 10.1038 / 35079077. [PubMed] [Cross Ref]
Van Den Oever MC, Goriounova NA, Li KW, Van Der Schors RC, Binnekade R., Schoffelmeer ANM, et al. (2008). Gwanin da ke gaba na gaba-da-gidanka Aikin mai saukin kamfani na AMPA yana da mahimmanci don sake komawa zuwa ga neman jinsin heroin. Nat. Neurosci. 11, 1053-1058. Doi: 10.1038 / nn.2165. [PubMed] [Cross Ref]
Vanderschuren LJ, Everitt BJ (2004). Rashin neman kwayoyi ya zama mai karfi bayan gwaninta mai kula da ciwon cocaine. Science 305, 1017-1019. Doi: 10.1126 / kimiyya.1098975. [PubMed] [Cross Ref]
Vezina P., Stewart J. (1990). Amfanin da aka yi amfani da shi a cikin yanki na kwakwalwa amma ba ga ƙwayar ƙwayar cuta ba ta haɓaka ƙananan ratsi zuwa tsarin morphine: rashin nauyin yanayi. Brain Res. 516, 99–106. doi: 10.1016/0006-8993(90)90902-N. [PubMed] [Cross Ref]
Vo N., Klein ME, Varlamova O., Keller DM, Yamamoto T., Goodman RH, et al. (2005). Sakamakon tsarin microRNA mai yalwaci mai karfi wanda ya kunshi nauyin ƙwayar cuta yana sarrafa tsarin kwayar neuronal morphogenesis. Shaida. Natl. Acad. Sci. Amurka. 102, 16426-16431. Doi: 10.1073 / pnas.0508448102. [PMC free article] [PubMed] [Cross Ref]
Walters CL, Blendy JA (2001). Bukatun daban-daban don amsar mayar da martani na CAMP a cikin ƙwayar cuta da kuma ƙwayar ƙarfafa kaddarorin magunguna na zalunci. J. Neurosci. 21, 9438-9444. [PubMed]
Wang J., Fang Q., Liu Z., Lu L. (2006). Yanayin yankuna na kwakwalwar kwakwalwa corticotropin-sakewa nau'in nau'in mai karɓar nau'in 1 a kan ƙuƙwalwa-damuwa- ko maganin ƙwayoyin cuta da aka farawa na maye gurbin morphine yanayin sanya wuri a cikin berayen. Psychopharmacology 185, 19–28. doi: 10.1007/s00213-005-0262-6. [PubMed] [Cross Ref]
Weiss F., Maldonado-Vlaar CS, Parsons LH, Kerr TM, Smith DL, Ben-Shahar O. (2000). Gudanar da halayyar hawan cocaine ta hanyar maganin miyagun ƙwayoyi a cikin berayen: sakamako akan sake dawo da matakan sarrafawa-mai amsawa da kuma karin bayani a cikin amygdala da ƙananan accumbens. Shaida. Natl. Acad. Sci. Amurka. 97, 4321-4326. Doi: 10.1073 / pnas.97.8.4321. [PMC free article] [PubMed] [Cross Ref]
Mai amfani A., Pescor FT (1967). Tsarin gargajiya game da wani abu mai kama da ƙwayar cututtuka na morphine, ƙarfafa hali na opioid da "sake dawowa" a cikin berayen morphine-kamu. Psychopharmacologia 10, 255-284. [PubMed]
Wolf ME, Tseng KY (2012). Wadanda suke karɓa da kwayoyin AMPA a cikin VTA da kuma tsakiya sune bayan haɓakar cocaine: a yaushe, ta yaya, kuma me ya sa? Gabar. Mol. Neurosci. 5:72. Doi: 10.3389 / fnmol.2012.00072. [PMC free article] [PubMed] [Cross Ref]
Wu X., Shi M., Wei C., Yang M., Liu Y., Liu Z., et al. (2012). Rashin yiwuwar ƙarfin synaptic da ƙwarewa mai zurfi a cikin ƙwayar ta tsakiya bayan da 10 kwanakin janyewar morphine. J. Neurosci. Res. 90, 1270-1283. Doi: 10.1002 / jnr.23025. [PubMed] [Cross Ref]
Young ST, Porrino LJ, Iadarola MJ (1991). Cocaine ta haifar da sunadarai c-fos-immunoreactive ta hanyar masu karɓa na D1 na dopaminergic. Shaida. Natl. Acad. Sci. Amurka. 88, 1291-1295. [PMC free article] [PubMed]
Zachariou V., Bolanos CA, Selley DE, Theobald D., Cassidy MP, Kelz MB, et al. (2006). Matsayi mai mahimmanci ga DeltaFosB a cikin tsakiya yana karawa cikin aikin morphine. Nat. Neurosci. 9, 205-211. Doi: 10.1038 / nn1636. [PubMed] [Cross Ref]
Zweifel LS, Argilli E., Bonci A., Palmiter RD (2008). Matsayi na masu karɓa na NMDA a cikin kwayoyin dopamine don nauyin haɗi da kuma haɓaka. Neuron 59, 486-496. Doi: 10.1016 / j.neuron.2008.05.028. [PMC free article] [PubMed] [Cross Ref]