Addiction: Rage hankalin sakamako da wardarin Swarewar Conswarewa Yana Consaddara don Overarfafa theungiyar Gudanar da inwayar Brain (2010)

Gabatarwa

Shekaru na 25 na ƙarshe na binciken bincike neuro sun samar da shaida cewa shan taba shine cututtuka na kwakwalwa, yana ba da hujja mai karfi don kiyaye irin wannan tsarin kula da lafiyar mutumin da aka kamu da shi kamar yadda yake da sauran cututtuka tare da babban tasirin jama'a, kamar ciwon sukari. Lalle ne, bincike kan jaraba ya fara gano abubuwan da suka faru da kuma abin da zai iya haifar da abin da zai iya haifar da mummunar cin zarafin abu. Wadannan binciken sun nuna yadda magungunan miyagun ƙwayoyi ke iya magance kwayoyin maɓalli da kwakwalwa, kuma hakanan ya rushe tsarin tafiyar da mafi girma wanda ke haifar da motsin zuciyarmu, cognition da hali. Mun koyi cewa jaraba yana nuna ta hanyar fadada sake zagayowar rashin aiki a kwakwalwa. Rashin lalacewar yakan fara ne a cikin juyin halitta mafi yawancin sassan kwakwalwa wanda ke aiwatar da sakamako, sa'an nan kuma ya motsa zuwa wasu yankunan da ke da alhakin ayyukan ƙwarewar da suka fi rikitarwa. Don haka, baya ga sakamako, mutane masu shan magani zasu iya samun haɓaka mai tsanani a koyo (ƙwaƙwalwar ajiya, sharaɗi, haɓakawa), aiki na zartarwa (ƙin yarda, yanke shawara, jinkirta jinkirin), fahimtar juna (fahimta) da ma tunanin (yanayi da damuwa haɓaka) ayyuka.

Yawanci daga sakamakon kwakwalwa na nazarin nazarin da ya yi amfani da sinadarin katsewar iska (PET), zamu gabatar da magungunan kwakwalwa wanda cutar ta ci gaba da yin amfani da kwayoyi, sa'an nan kuma gabatar da samfurin da ya dace, bisa ga abin da akidar ta haifar da sakamakon sakamakon yin amfani da bayanai a cikin kuma cikin wadannan jigilar. Binciken da aka fahimta game da waɗannan matakan kwakwalwa na nakasassu (na neuroplastic), da kuma abubuwan da ke tattare da muhalli da yanayin muhalli wanda ke tasiri akan yiwuwar su, yana da matukar muhimmanci ga ci gaba da inganta rigakafi da hanyoyin magance maganin rigakafi.

Babban, amma takaice, buƙatar dopamin ana buƙata don jaraba

Addiction shine, da farko kuma mafi mahimmanci, cuta ce ta tsarin sakamako na ƙwaƙwalwa. Wannan tsarin yana amfani da kwayar cutar neurotransmitter dopamine (DA) a matsayin babbar kuɗaɗen kuɗaɗen ta don watsa bayanai. Brain DA na taka muhimmiyar rawa wajen sarrafa bayanai game da jin dadi [1, 2], wanda yake a zuciyarsa na iya tsarawa ko tasiri sakamako [3, 4], sa ran sakamako [5], motsawa, motsin rai, da jin daɗin rayuwa. Saukewar DA na ɗan lokaci a cikin kwakwalwar kwakwalwa ya zama dole, duk da cewa bai isa ba, abin da ya faru a cikin rikitarwa wanda ke haifar da jin daɗi na sakamako: ƙaruwa cikin DA ya zama yana da alaƙa da ƙarfin “babban” abin da batutuwa ke fuskanta. Ana bayar da martani ne kawai idan aka sake sakin DA a matsayin waɗannan kaifi, wucin gadi, hauhawa, don amsa magunguna ko alamun alaƙa da magunguna.

Abin sha'awa, a kai tsaye ko a kaikaice, dukkanin kwayoyi masu amfani da ƙwayoyi suna aiki ta hanyar haifar da ƙari amma ƙari yana ƙaruwa a cikin extracellular DA a cikin wani ɓangaren maɓallin sakamako (limbic) tsarin [6, 7], musamman, a cikin ƙananan ƙwayoyin (Nac) dake cikin kwakwalwa. Irin wannan nau'in DNA yana kama, kuma a wasu lokutta sun fi girma, ilimin lissafi yana ƙaruwa ne ta hanyar bunkasa yanayin da ake ciki (wanda ake kira a matsayin ƙarfafawa ko dabi'a). Kamar yadda zamu yi tsammanin, kwakwalwa na kwakwalwar mutum ta hanyar yin nazari ta hanyar yin amfani da linzamin kwance (PET), ya nuna cewa DA ya karu da nau'o'in kwayoyi (misali. masu tasowa (Fig. 1A), [8, 9], nicotine [10], da barasa [11]) a cikin kwakwalwa na kwakwalwa, ana danganta su da ilimin da aka yi na euphoria (ko babba) yayin shan giya [12, 13, 14]. Tun da nazarin PET za a iya yi a cikin shahararren ɗan adam mutane kuma yana yiwuwa a yi la'akari da dangantakar dake tattare da rahotannin rahotanni game da maganin miyagun ƙwayoyi da kuma sauyawar matakan DA. Yawancin bincike sun ruwaito cewa wadanda suke nuna yawan ci gaba da aka samu a bayan maganin miyagun ƙwayoyi [amphetamine, nicotine, barasa, methylphenidate (MPH)] kuma sun bayar da rahoton mafi girma ko tsayi (Fig. 1B).

Ilimin dabbobi da ɗan adam sun nuna cewa gudun da kwayar cutar ta shiga, tana aiki, kuma tana barin kwakwalwa (ie bayanin kamfanonin pharmacokinetic) yana taka muhimmiyar rawa a cikin kayyade tasirin ƙarfafawa. Lalle ne, kowace miyagun ƙwayoyi da aka yi wa kwakwalwa da kwakwalwa da kwayoyin cutar ta PET (cocaine, MPH, methamphetamine, da nicotine) suna nuna irin wannan bayanin yayin da gwamnati ta kasance cikin intravenous, ie, matakai mafi girma a cikin kwakwalwar mutum sun kai a cikin 10 min (Fig. 2A) kuma wannan azumi mai sauri yana hade da "high" (Fig. 2B). Bisa ga wannan ƙungiyar, yana biye da cewa tabbatar da cewa miyagun ƙwayoyi ya shiga cikin kwakwalwa a hankali kamar yadda ya kamata ya zama hanya mai mahimmanci wajen rage ƙarfin ƙarfafawa, saboda haka yana da alhaki. Mun tsara wani gwaji don gwada wannan jigilar ta tare da MPH mai ƙyama, wadda, kamar cocaine, ta ƙara DA ta hanyar rage jinkirin saukar da shi zuwa cikin neuron presynaptic (ie ta hanyar kulle DA masu watsawa), saboda haka yana ƙarfafa siginar DA. Lalle ne, mun gano cewa, yayin da gwamnatin intravenous na MPH sau da yawa euphorigenic, MPH da aka gudanar da magana, wanda ya kara ƙaruwa DA a cikin striatum [15], amma tare da 6- zuwa 12-ninka kamfanonin pharmacokinetics masu saurin hankali, ba a gane su da yawa kamar ƙarfafawa [16, 17]. Saboda haka, rashin nasara na MPH - ko amphetamine [18] ga wannan lamarin - don haifar da wani babban abu mai yiwuwa shine tunani na jinkirta shiga cikin kwakwalwa [19]. Saboda haka, yana da kyau a bada shawara akan kasancewa tsakanin kuskuren tsakanin layin da miyagun ƙwayoyi ke shiga cikin kwakwalwa, wanda ya ƙayyade gudun da DA ke ƙaruwa a cikin kwakwalwa, da kuma tasirin ƙarfafa [20, 21, 22]. A wasu kalmomi, don maganin miyagun ƙwayoyi don yin ƙarfin haɓakawa dole ne ta tada DA abruptly. Me yasa hakan ya kasance haka?

Bisa ga girman da tsawon lokacin harbe-harben neuronal, DA nunawa zai iya ɗauka daya daga cikin siffofin biyu: phasic ko tonic. Alamar Phasic yana nuna babban ƙarfi da gajeren fashewa, yayin da alamar tonic yana da mahimmancin ƙararrawa da kuma karin lokaci. Bambanci yana da mahimmanci saboda yana nuna cewa samfurin DA ya nuna wajibi ne don magungunan zalunci don haifar da "maganganun da aka damu," wanda shine daya daga cikin kwakwalwa na farko wadanda suka biyo bayan maganin cigaba (ciki har da magani). Ɗaya daga cikin siffofin da ke tattare da alamar alamar alama da kwanciyar hankali shine shigar da D2R da glutamate n-methyl-d-aspartic acid (NMDA) masu karɓa [23]. A wani ɓangaren kuma, alamar tonic DA tana taka muhimmiyar rawa a cikin yanayin yin aiki da ƙwaƙwalwar ajiya da sauran matakan gudanarwa. Wasu daga siffofin da ke rarrabe wannan yanayin na alama daga nau'in siffa shine cewa yana aiki mafi yawa ta hanyar ƙarancin DA DA masu karɓa (DA D1 masu karɓa). Duk da haka, kuma duk da bambancin hanyoyin da ke tattare da su, yaduwar magungunan miyagun ƙwayoyi (da canje-canje a cikin tashar DA ta hanyar tasiri ta hanyar waɗannan masu karɓa) an haɗa su a cikin canje-canjen neuroplastic da zasu haifar da kwaskwarima [25] ta hanyar gyaran NMDA da alpha-amino-3-hydroxyl-5-methyl-4-isoxazone-propionate (AMPA) masu karbawan glutamate [24].

Shaidun ya nuna cewa miyagun ƙwayoyi-induced ƙarawa a DA mimic phasic DA cell firing. Wannan yana taimakawa wajen yin bayanin dalilin da yasa amfani da jima'i na yau da kullum zai iya haifar da irin wannan maganganun da ya dace da maganin miyagun ƙwayoyi, da tsammaninsa, da kuma ra'ayoyin mutane (mutane, abubuwa da wurare) da suka haɗa da amfani. Duk da haka, yayinda matsalolin magungunan magungunan da ake amfani da su akan magunguna da suka dogara da irin azabar da aka samu DA ƙarawa "wajibi ne" don ci gaba da jaraba, to babu shakka ba "isasshe ba". ci gaba saboda suna haifar da ƙananan neuroadaptations a wasu tsarin neurotransmitter (misali glutamate [26] kuma watakila kuma γ-aminobutyiric acid (GABA)), wanda, ƙarshe, ya shafi ƙarin kwakwalwar kwakwalwa wanda DA ya tsara. Wadannan hanyoyin suna mayar da hankali ga sashe na gaba.

Yin amfani da miyagun ƙwayoyi na yau da kullum ya ɓad da masu karɓar kwayoyin dopamine da kuma samar da dopamine: An ƙaddara "high"

Gaskiyar cewa yin amfani da miyagun ƙwayoyi dole ne ya zama daɗaɗɗɗa kafin jaraba yana da tushe shi ne alamar nuna cewa cutar ta samo asali ne, a cikin mutane masu ƙyama, a kan maimaita matsalar tsarin lada. Wadannan rikicewa zasu iya haifar da neuroadaptations a wasu sauran hanyoyi (dalili / kullin, iko mai hanawa / zartarwa, da ƙwaƙwalwar ajiya / kwandishan) wanda kuma DA [27]. Daga cikin kwakwalwar da aka ba da labarin a cikin batutuwa da aka yi amfani da su shine manyan raguwa a cikin matakan da masu karɓa na D2R (high affinity) da kuma adadin DA sun fito da kwayoyin DA [28] (Siffa 3). Abin mahimmanci, waɗannan raguwa suna haɗuwa da ƙananan ƙauraran yanki na yanki a yankunan kodayake na gaba (PFC) waɗanda ke da mahimmanci don yin aiki nagari (ie Gyrus cingulate na baya (CG) da kuma orbitofrontal cortex (OFC)) (Fig. 4A). Wannan kallo ya jagoranci mu mu aika cewa wannan na iya kasancewa daya daga cikin hanyoyin da ke haɗuwa da ƙaddamar da miyagun ƙwayoyi a DA tare da yin amfani da miyagun ƙwayoyi na miyagun ƙwayoyi da kuma rashin kulawa da yin amfani da miyagun ƙwayoyi waɗanda ke nuna jaraba [29]. Har ila yau, sakamakon haifar da cutar hypodopaminergic zai yi bayani game da raunin da mutum ya kamu da shi game da kyaututtuka na halitta (misali abinci, jima'i, da sauransu) da kuma dawwamar da amfani da miyagun kwayoyi a matsayin hanyar biyan diyyar wannan rashi na dan lokaci [30]. Wani muhimmin bayani game da wannan ilimin shi ne cewa magance wadannan ƙarancin (ta hanyar ƙara D2R matakan da kuma ƙara DA saki a cikin yankunan striatum da yankuna na farko) zai iya bayar da wata hanyar da za a iya magance magunguna [31]. Shin akwai wata shaida da cewa juyawa da yanayin hypodopaminergic zai iya samun tasiri mai tasiri akan halayen magunguna? Amsar ita ce a. Ayyukanmu sun nuna cewa ta hanyar tilasta haɓakawa na D2R, cikin zurfin tsarin hawan cocaine- ko giya masu shan barasa, za mu iya rage yawan gwanin cocaine [31] ko barasa [32], bi da bi. Bugu da ƙari, a rodents, da kuma a cikin mutane methamphetamine abusers [33], matakin ƙananan matakin D2R kuma yana hade da impulsivity, kuma a cikin rodents ya tsinkaye alamu na barazanar kula da miyagun ƙwayoyi (duba ƙasa).

Hakanan binciken binciken ya nuna cewa, a cikin mutane, jaraba yana haɗuwa da raguwar DA DA a cikin sassan kwakwalwa da kuma wasu yankuna na striatum, kuma a cikin maganganun da suka dace da miyagun ƙwayoyi a cikin aiki da kuma masu amfani da magungunan ƙwayoyi (Siffa 5) [34]. Wannan wani bincike ne da ba a sani ba tun lokacin da aka tsinkaye shi cewa jaraba ya nuna karfin haɓakawa ga sakamako (sabili da haka sakamakon maganin maganin). A magungunan miyagun ƙwayoyi, ragewa a DA release zai iya nuna ko dai disrupted neurophysiology a cikin sakamako circuitry (ie a cikin DA neurons cewa saki DA a cikin striatum) ko kuma, a madadin haka, wata ka'ida ta jujjuyawar da aka yi ta hanyar ladaran ta hanyar gaba daya (jagora mai sarrafawa) ko hanyoyin amygdalar (tunanin zuciya) (hanyar da aka fara amfani da amygdalarstriatal glutamatergic). Tun lokacin da aka yi amfani da kwayar cutar kwayar cuta a cikin striatum, kamar yadda aka gani a cikin magungunan miyagun ƙwayoyi na yau da kullum, ba ya kula da dabi'un da ke nuna halayyar cin zarafi, kamar impulsivity, cravings, da sake sakewa da magungunan miyagun ƙwayoyi ke haifarwa, da kuma amygdala) suna da hannu a nan, saboda rushewarsu zai taimaka ko akalla rinjayar waɗannan dabi'un halaye.

Rashin karɓan lamarin dopamine (DR2) ba shi da tasiri akan ikowar impulsivity ta hanyar kututture na gaba

An yi tsammanin cewa maye gurbi akan miyagun ƙwayoyi masu karfi da ke halayyar halayya wanda ke nuna jaraba yana iya zama a cikin wani ɓangare na dysfunctions musamman a yankuna na gaba na kwakwalwa [35]. Akwai shaidu mai yawa da ke goyan bayan wannan ra'ayi, farawa da nazarin dabba wanda ke gano hanyar haɗi tsakanin D2R da kuma halayyar halin kirki. Gwaje-gwajen da berayen suna nuna alamar daidaituwa tsakanin low D2R da impulsivity [36], da kuma tsakanin impulsivity da shugabancin miyagun ƙwayoyi [37]. Amma menene haɗin? Kamar yadda aka ambata, a cikin magungunan miyagun ƙwayoyi, D2R mai tsanani ya fi dacewa da ƙwayar glucose a cikin ƙananan yankuna na PFC, irin su OFC (wanda ke da alamar halayyar salience kuma wanda aka rushe shi ya haifar da halayen halayen) kuma a CG (wanda ke da iko tare da kuma kuskuren ɓatawa kuma wanda rushewa ya haifar da impulsivity) (Fig. 4B) [38, 39]. Bugu da ƙari, a cikin wani binciken da muka yi a cikin mutane (yana nufin shekaru SD ±, 24 ± 3 shekaru) tarihin tarihin shan giya, amma wadanda ba su da giya ba, mun kuma gano wani muhimmiyar ƙungiya tsakanin D2R da kuma metabolism a yankuna na gaba (CG , OFC, da kuma PFC mafi girma) kuma a cikin tsohuwar insula (da ke cikin hulɗar yanar-gizon, fahimtar kai, da kuma jin dadi)40] (Siffa 6). Abin sha'awa, wa] annan mutanen suna da D2R mafi girma fiye da yadda aka yi amfani da su ba tare da tarihin iyalin shan giya ba, kodayake ba su bambanta ba a gaban dabara. Har ila yau, a cikin sarrafawa, D2R mai dadi ba ya daidaita tare da metabolism na gaba. Wannan ya haifar da muyi tunanin cewa mafi girma daga D2R na al'ada a cikin batutuwa da ke dauke da mummunar haɗari ga maye gurbi sun kare su daga shan giya a wani bangare ta hanyar ƙarfafa ayyukan a yankuna na gaba. Lokacin da aka haɗu, waɗannan bayanai sun nuna cewa matakai masu girma na D2R a cikin striatum na iya kare kariya daga zubar da ƙwayoyi da kuma jaraba ta hanyar kiyaye dabi'un impulsivity a karkashin iko, ie, ta hanyar tsara tsarin da ke tattare da hana haɓakar halayyar hali da kuma sarrafa motsin zuciyarmu.

Hakazalika, mun yi tsammanin cewa yankunan da ke gaba da su suna da hannu wajen raguwa da sakin labaran DA (da kuma ƙarfafawa) a cikin batutuwa masu jituwa tun lokacin da suka tsara DA kamfanonin wayar da ke cikin tsakiya da kuma DA a saki. Don gwada wannan jaddada zamu tantance dangantakar dake tsakanin kwakwalwa a cikin PFC da kuma karuwa a cikin DA DA ya jawowa ta hanyar MPH a cikin sarrafawa da masu maye gurbi. Daidai da tsinkaya, a cikin masu maye gurbin mun kasa gano ƙungiyar ta al'ada ta tsakanin magungunan farko da aka ba da shi da kuma DA a cikin striatum, suna nuna cewa alamar da aka yi a cikin DA release a cikin striatum da aka gani a cikin masu shan giya suna nuna wani ɓangare mara kyau na ka'idar kwakwalwa ta hanyar kwakwalwa ta tsakiya [34].

Saboda haka, mun sami wata ƙungiya tsakanin raguwar ƙaura a cikin PFC da rage D2R mai tsanani a cikin batutuwa masu maganin miyagun ƙwayoyi, da kuma tsakanin aikin PFC da aka fara da DA sakewa a cikin sarrafawar da ba a cikin wadanda aka kamu ba. Wadannan ƙungiyoyi sun haifar da haɗin haɗakar da ke tsakanin ƙananan hanyoyi a cikin hanyoyin PFC da kuma dysfunctions a ƙasa a cikin tsarin DA da ladabi, mai yiwuwa saboda rinjayar PFC akan impulsivity da compulsivity. Duk da haka, waɗannan ba su da lissafi don ƙarin halin halayen hali, irin su sakamakon alamun da ake haɗar da miyagun ƙwayoyi a cikin sha'awar sha'awa, wanda zai watsi da ƙwaƙwalwar ajiya da kuma ilmantarwa.

Sakamakon yanayin da yanayin stereotypic ya maye gurbin "high" a matsayin direba

Ƙarfafawa daga cikin kwayoyin DN a cikin kwakwalwa ta ƙarshe ya kafa sabon haɗin aiki a cikin kwakwalwa tsakanin aikin haɗakar da ƙwaƙwalwar, da kuma yanayin da ke kewaye da shi (misali, yanayi, na yau da kullum na shirya miyagun ƙwayoyi, da sauransu), ƙaddamar da sabuwar , ƙungiyoyi masu ilmantarwa waɗanda zasu iya haifar da hali. Daga qarshe, kawai ƙwaƙwalwar ajiya ko tsammani na miyagun ƙwayoyi zai iya haifar da halayen halin haɓaka wanda ya dace da mutane. Tare da yin amfani da miyagun ƙwayoyi akai-akai, ƙaddamar da kwayoyin DA a cikin striatum sun fara canza musayar neurochemistry da ke tattare da haɗin kai. Wannan yana taimakawa wajen ƙarfafa ƙwaƙwalwar ƙwaƙwalwar ƙwayoyin cuta da aka haɗa da miyagun ƙwayoyi, wanda ke taimakawa wajen bayyana yiwuwar dukkanin maganganu masu haɗari da ƙwayoyi (a cikin koyi na samun karbar magani lokacin da aka nuna su a cikin wadannan matsalolin) [41] don sau da yawa faɗar DA cell firing. Kuma saboda tasirin DA a cikin dalili, wadannan DA ƙara ƙarfafa motsawar motsi da ake buƙata don samun lada [42]. Lalle ne, lokacin da aka nuna ratsi sau da yawa zuwa wani motsi mai tsaka tsaki wanda aka haɗa tare da miyagun ƙwayoyi (sharaɗi), zai iya haifar da ƙarawar DA kuma ya sake inganta tsarin kula da miyagun ƙwayoyi [43]. Irin wadannan maganganun da suke da kwaskwarima suna da kyau a cikin ƙwayoyin cuta don suna da alhakin yiwuwar wani mutumin da ya kamu da shi ya sake dawowa ko da bayan lokuta na detoxification. A halin yanzu, kwakwalwar kwakwalwar fasaha ta ba mu damar gwada ko yaduwar mutane zuwa alamun da ake haɗuwa da miyagun ƙwayoyi na iya jawo hankalin miyagun ƙwayoyi kamar yadda aka nuna a cikin dabbobi masu labaran.

Tare da yin amfani da miyagun ƙwayoyi akai-akai, ƙaddamar da kwayoyin DA a cikin striatum sun fara canza musayar neurochemistry da ke tattare da haɗin kai. Wannan yana taimakawa wajen ƙarfafa ƙwaƙwalwar ƙwaƙwalwar ƙwayoyin cuta da aka haɗa da miyagun ƙwayoyi, wanda ke taimakawa wajen bayyana yiwuwar dukkanin maganganu masu haɗari da ƙwayoyi (a cikin koyi na samun karbar magani lokacin da aka nuna su a cikin wadannan matsalolin) [41] don sau da yawa faɗar DA cell firing. Kuma saboda tasirin DA a cikin dalili, wadannan DA ƙara ƙarfafa motsawar motsi da ake buƙata don samun lada [42]. Lalle ne, lokacin da aka nuna ratsi sau da yawa zuwa wani motsi mai tsaka tsaki wanda aka haɗa tare da miyagun ƙwayoyi (sharaɗi), zai iya haifar da ƙarawar DA kuma ya sake inganta tsarin kula da miyagun ƙwayoyi [43]. Irin wadannan maganganun da suke da kwaskwarima suna da kyau a cikin ƙwayoyin cuta don suna da alhakin yiwuwar wani mutumin da ya kamu da shi ya sake dawowa ko da bayan lokuta na detoxification. A halin yanzu, kwakwalwar kwakwalwar fasaha ta ba mu damar gwada ko yaduwar mutane zuwa alamun da ake haɗuwa da miyagun ƙwayoyi na iya jawo hankalin miyagun ƙwayoyi kamar yadda aka nuna a cikin dabbobi masu labaran.

An bincika wannan tambaya a cikin masu cin zarafin cocaine. Amfani da PET da [¹¹C] raclopride, binciken bincike na biyu ya nuna cewa bayyanar da hotuna mai sanyaya (game da maganin cocaine mai shan taba) amma ba zuwa bidiyon da ba ta da tsaka-tsakin (yanayin yanayi) ya karu DA a cikin 'yan Adam da ke cikin cocaine (Siffa 7) da kuma cewa DA ƙarawa sun haɗu da rahotanni na asali game da ciwon magunguna [44, 45]. Mafi girman DA yana ƙarawa ta hanyar daukan hotuna ta hotuna, kamar yadda ƙananan miyagun ƙwayoyi suke. Bugu da ƙari, ƙarfin ƙaruwar DA ya haɓaka da ƙananan ƙwaƙwalwar ƙwayar cuta, yana nuna muhimmancin maganganun da aka yi a cikin asibiti.

Yana da muhimmanci muyi jaddada cewa, duk da irin ƙarfin da ake yi na waɗannan ƙungiyoyi masu ɓarna, mun tattara kwanan nan da sababbin shaidun da ke nuna cewa masu cin zarafin cocaine suna riƙe da wasu ƙwarewa don hana hauka. Saboda haka, dabarun da za su karfafa ka'idojin gaba-gaba za su iya ba da damar amfani da cututtuka [46].

Tunzura shi gabã ɗaya

Wasu daga cikin abubuwa masu lalata da ƙwayar magungunan ƙwayoyi suna da sha'awar yin amfani da kwayoyi wanda zai iya sake dawowa bayan bayan shekaru da yawa, da kuma yiwuwar ƙwaƙwalwar da mutane ke da shi don hana miyagun ƙwayoyi da ke nema bayan da sha'awar ta ɓoye duk da sanannun sakamakon da ya faru.

Mun gabatar da samfurin jaraba [47] wanda ya bayyana yanayin yanayin wannan cuta ta hanyar samar da hanyar sadarwar hanyoyin sadarwa guda huɗu, wanda haɗin gwiwar haɗin gwiwar zai iya bayyana da dama daga cikin siffofin siffar stereotypic na jaraba: (a) sakamako, ciki har da da yawa daga cikin ƙananan ganglia, musamman ma ventral striatum, wanda Nac ya karbi labari daga yankin na kwakwalwa na kwakwalwa kuma ya sake fadin bayanin zuwa ga pallidum (VP); (b) motsawa / kullun, wanda ke cikin OFC, gurguntaccen ƙwayar cuta, dorsal striatum da man fetur; (c) ƙwaƙwalwa da kuma ilmantarwa, dake cikin amygdala da hippocampus; da (d) tsarawa da kuma sarrafawa, wanda ke cikin magungunan farko, wanda ke gaba da CG da ƙananan bala'i na baya. Wadannan jiguna huɗun suna karɓar dasu daga kai tsaye daga DA neurons amma suna haɗawa da juna ta hanyar hanzari kai tsaye (ko mafi yawan glutamatergic).

Hanyoyi huɗu a cikin wannan tsari suna aiki tare kuma ayyukansu sun canza tare da kwarewa. Kowane an haɗa shi da wani muhimmin mahimmanci, kamar haka: jinƙan (sakamako), na gida (motsawa / drive), ƙungiyoyi masu koya (ƙwaƙwalwar ajiya, shararwa), da rikici (iko). Bugu da ƙari, waɗannan ma'anar suna hulɗa da ƙungiyar da take ciki tare da yanayi (ciki har da haɓakar haɓaka) [48] da kuma tare da hulɗar yanar gizo (wanda ke haifar da sanarwa game da sha'awar miyagun ƙwayoyi da yanayi) [49]. Mun ba da shawara cewa tsarin aiki a cikin hanyar sadarwa huɗu da aka kwatanta a nan yana tasiri yadda mutum na al'ada ya sa zaɓuɓɓuka tsakanin masu hamayya. Wadannan zaɓuɓɓukan suna rinjaye su ta hanyar lada, ƙwaƙwalwar ajiya / kwanto, motsi, da kuma hanyoyin sarrafawa kuma waɗannan biyun suna tsara su ta hanyoyi masu rai da fahimta (Fig. 8A).

Amsar da take da shi ta hanyar jin dadi yana da nasaba da jin dadi na dan lokaci, watau sakamakon sa ransa. Hakanan, ana sa ran sakaci a cikin sashi ta hanyar DA neurons da ke shiga cikin kwakwalwa na kwakwalwa da kuma rinjaye da ƙaddamarwa daga OFC (wanda ke ba da darajar salula a matsayin mahallin mahallin) da amygdala / hippocampus (wanda ke da mahimmancin martani da ƙwaƙwalwar ajiyar ƙwaƙwalwa). Tamanin abin da ke cikin motsa jiki yana da nauyi (idan aka kwatanta) da sauran matsalolin matakan, amma yana canzawa a matsayin aiki na bukatun na mutum, wanda aka lalace ta yanayi (ciki har da haɓakar haɓaka) da kuma fahimtar fahimtar juna. Musamman, maganin yalwata yana inganta ƙimar ƙwayar magungunan kwayoyi yayin da lokaci ɗaya ya rage tsarin ka'idoji na amygdala [50]. Bugu da ƙari, tun da yawancin halayen miyagun ƙwayoyi suna danganta da haɓaka ingantattun abubuwan da za su iya magance matsalolin da ke tattare da wannan dalilin dalilin da yasa danniya zai iya haifar da sake dawowa da miyagun ƙwayoyi sau da yawa a yanayi na asibiti. Ƙin ƙarfafa nauyin ƙwarewar abin da ke cikin motsa jiki, a cikin wani ɓangare mai siffar da abubuwan da suka faru na baya, wanda ya fi ƙarfin shigar da na'urar motsa jiki kuma ya fi ƙarfin kullin don samo shi. Ƙaƙarin shawara na yin aiki (ko a'a) don samun samfurin yana aiki ne ta hanyar PFC da CG, wanda ya auna ma'auni tsakanin mahimmanci mai kyau da sakamakon sakamako marar jinkiri, da kuma ƙananan ƙarancin gaba (Broadmann Area 44), wanda ke aiki don hana ƙaddamarwar amsawa ga aiki [51].

Bisa ga wannan samfurin, a cikin abin da aka kamu (Fig. 8B), ana amfani da muhimmancin amfani da miyagun ƙwayoyi na zalunci da kuma alamomin da aka haɓaka a sakamakon wasu sakamako (na halitta), wanda aka rage girmansa. Wannan zai bayyana dalilin da ya sa ya nemi motsa jiki. Duk da haka, mummunan ƙwaƙwalwar magungunan miyagun ƙwayoyi yana sake samun ladaran ƙofofin, wanda hakan zai haifar da rageccen ƙwarewar ladaran ladaran ga masu ƙarfafawa [52], wanda ma yana taimakawa wajen bayyana darajar rage yawan masu taimakawa magungunan miyagun ƙwayoyi a cikin mutum mai kamu. Wani dalili na ingantaccen ƙwarewar maganin miyagun ƙwayoyi shine rashin daidaituwa na DA na magance magunguna (haƙuri) idan aka kwatanta da al'ada na al'ada da ke samuwa ga sakamakon ladabi kuma hakan yana haifar da jin dadi [53].

Bugu da ƙari, ɗaukar hotuna zuwa matsalolin kwakwalwa yana isasshen ƙãra ƙimar alamun [54]; Ta haka ne, zamu yi tsammani cewa a cikin wani mutum da ya kamu da kamu, yana nunawa ga yanayin da yanayin da ya dace ya kara ƙarfafa yawan hankali da aka ba su. Idan ba'a samu gasar ba daga wasu masu ƙarfafawa, ilmantarwa na kwaskwarima yana ƙarfafa samun ƙwayar miyagun ƙwayoyi zuwa matakin babban motsi na mutum. Muna tsammanin cewa samfurin magani (ko danniya) zai haifar da azumi DA ƙarawa a cikin Nac a cikin kwakwalwa na kwakwalwa kuma a cikin dorsal striatum wanda ke motsa dalili don daukar magani kuma rashin lafiyar PFC ba zai iya magance shi ba. Saboda haka, a kan amfani da miyagun ƙwayoyi da kuma maye gurbin da alamomin DA ɗin zasu haifar da kwarewar kwarewa / kwarewa da ƙwaƙwalwar ajiya, wanda ya kashe PFC (ƙinƙarar farko yana faruwa tare da ƙarawa amygdala)50], tare da hana ikon PFC don sarrafa tsarin motsa jiki / motsa jiki. Idan ba tare da wannan hani ba, to an tabbatar da ƙwaƙwalwa mai tushe, wanda zai haifar da ciwon miyagun ƙwayoyi. Saboda haɗuwa tsakanin kewayoyin suna aiki ne, da kunna hanyar sadarwa a yayin maye gurbi ya taimaka wajen ƙarfafa ƙimar magungunan miyagun ƙwayoyi da kuma kwantar da hankali ga magunguna.

karshe

A takaice dai, muna ba da samfurin da yake lissafin asibiti kamar haka: A lokacin jaraba, ƙimar ingantaccen magungunan ƙwayoyin cuta a cikin ƙwaƙwalwar ƙwaƙwalwar ajiyar tana tafiyar da sakamako kuma yana ƙarfafa motsawa don cinye miyagun ƙwayoyi, ta cinye ikon sarrafawa wanda PFC ya riga ya dashi. Kodayake yawan karuwar kwayar cutar DA ya haifar da hankali a cikin batutuwa masu maganin miyagun ƙwayoyi, maganin maganin maganin maganin magani ya zama abin da ya dace a cikin kansu, ya kara motsawa don daukar magani kuma yana mai da hankali ga ƙwaƙwalwar amsawa ta yanzu ba tare da ɓoye ba, saboda cirewa na tsarin kulawa na farko. Bugu da kari, jaraba zai iya sake tsara abubuwan da suke tattare da yanayi da fahimtar juna (wakilai masu duhu)Fig. 8B) a cikin hanyoyi da, idan gwagwarmayar da aka gwada, za su kara da ma'auni daga kulawar hanawa da kuma yin amfani da miyagun ƙwayoyi.

Mun yarda da cewa wannan samfuri ne mai sauƙi: Mun gane cewa wasu yankuna na kwakwalwa dole ne su shiga cikin wadannan rukunin, wanda yankin zai iya taimakawa zuwa wasu hanyoyi, kuma sauran sassa zasu iya shiga cikin jaraba. Bugu da ƙari, ko da yake wannan samfurin ya mai da hankalin DA, ya tabbata daga ƙididdiga na musamman cewa gyare-gyare a cikin matakan da aka yi amfani da shi a cikin hanzari ya janyo hanyoyi da dama da aka lura a cikin jaraba kuma mun tattauna a nan. Har ila yau, ya bayyana daga ilimin ƙididdigar cewa wasu masu amfani da kwayoyin suna shiga cikin maganin maganin magunguna ciki har da cannabinoids da opioids. Abin takaici, har zuwa kwanan nan, iyakanceccen damar yin amfani da rediyon rediyo na PET ya ƙayyade damar da za a bincika shigar da wasu masu amfani da labaran magani a cikin labaran magani kuma a cikin buri.

gajartatattun