Methamphetamine yayi aiki a kan ƙananan ƙananan hanyoyi waɗanda ke tsara halayyar jima'i a cikin ratsan mata (2010)

Neuroscience. 2010 Mar 31; 166 (3): 771-84. Doi: 10.1016 / j.neuroscience.2009.12.070. Epub 2010 Jan 4.

Frohmader KS, Hikimar J, Mai hikima RA, Lehman MN, Coolen LM.

source

Ma'aikatar Anatomy da Cell Biology, Cibiyar Medicine da Dentistry na Schulich, Jami'ar Western Ontario, London, ON, Kanada, N6A 5C1.

Abstract

Methamphetamine (Meth) yana da karuwa sosai. Hada cin zarafin Meth yana hade da halayyar haɗarin jima'i da ƙara yawan ƙwayar cutar ta Mutum da kuma masu amfani da Meth suna nuna sha'awar jima'i, haɓaka, da kuma jima'i. Ka'idar nazarin halittu don wannan jima'i-jima'i nexus ba a sani ba. Binciken na yanzu ya nuna cewa tsarin Meth a cikin ratsan namiji yana aiki ne a cikin sassan kwakwalwa na tsarin mesolimbic wanda ke cikin ka'idojin halayyar jima'i. Musamman, Meth da mating co-activate cells a cikin tsakiya accumbens core da harsashi, amygdala basolateral, da kuma tsohon cingulate cortex. Wadannan binciken sun nuna cewa da bambanci da maganganu na yaudara na yaudara za su iya kunna wannan kwayoyin halitta a matsayin mai taimakawa na al'ada, wannan shine halayyar jima'i, kuma daga bisani zai iya tasiri ga neman neman wannan sakamako na hakika.

keywords: ƙananan ƙwayoyin cuta, amygdala masu ɗamara, magungunan farko, maganin abu, haifuwa, jaraba

Ƙarfafawa da ladabi an tsara su ta hanyar tsarin mesolimbic, cibiyar sadarwar da ke cikin kwakwalwa ta ƙungiyar kwakwalwa (VTA) ta tsakiya (NAc), amygdala mai bastoral, da kuma matakan farko na mota (mPFC)Kelley, 2004, Kalivas da Volkow, 2005). Akwai cikakke shaidar cewa ana amfani da tsarin mesolimbic a mayar da martani ga duka abubuwa na zagi (Di Chiara da Imperato, 1988, Chang et al., 1997, Ranaldi et al., 1999) da kuma ta hanyar dabi'a masu ladabi irin su halin jima'i (Fiorino et al., 1997, Balfour et al., 2004). Halin jima'i na jima'i, da mawuyacin yanayi, yana da karfin gaske kuma yana karfafawa a cikin samfurori na dabbobi (Pfaus et al., 2001). Ma'aikatan rani suna ci gaba da zaɓi na musamman (CPP) don magancewa (Agmo da Berenfeld, 1990, Martinez da Paredes, 2001, Tenk, 2008), kuma za su yi ayyuka masu aiki don samun damar yin amfani da mace mai karɓar jima'i (Everitt et al., 1987, Everitt da Stacey, 1987). Magunguna na cin zarafi suna da ladabi da ƙarfafawa, kuma dabbobi zasu koyi yadda za a magance duk wani mummunar lalacewa, ciki har da masu amfani da kwayoyi, da nicotine, da barasa,Mai hikima, 1996, Pierce da Kumaresan, 2006, Feltenstein da Duba, 2008). Ko da yake an san cewa duka magungunan magunguna da halayyar jima'i suna aiki da wuraren kwakwalwa na mesolimbic, yanzu ba a san ko magungunan zalunci na shafar irin wannan igiya da ke yin rikici ba.

Nazarin ilimin ilmin lissafi ya nuna cewa abinci da cocaine duka suna aiki ne a cikin NAc. Duk da haka, masu ƙarfafawa biyu ba su kunna wannan kwayar halitta a cikin NAc ba (Carelli et al., 2000, Carelli da Wondolowski, 2003). Bugu da ƙari, cin abinci da sukayi na mulkin soja ba sa haifar da canje-canje na lokaci mai tsawo na gine-ginen electrophysiological kamar yadda ake haifar da cocaine (Chen et al., 2008). Sabanin haka, tarin shaidun shaida yana nuna cewa halayyar jima'i da magungunan zalunci za su iya yin aiki a kan nau'ikan nau'ikan mesolimbic guda. Masu bautar gumaka da haɓakawa suna canza yanayin nuna halayen jinsi a cikin jinsi maza (Mitchell da Stewart, 1990, Fiorino da Phillips, 1999a, Fiorino da Phillips, 1999b). Bayanan kwanan nan daga jaridarmu sun nuna cewa jima'i yana canzawa da amsa ga likitoci na jiki kamar yadda aka nuna ta hanyar maganin locomotor da aka fahimta da kuma fahimtar fahimtar lada ga d-amphetamine a cikin dabbobin jima'i da jima'i (Pitchers et al., 2009). An gano irin wannan amsa irin wannan lokaci tare da nunawa ga amphetamine ko wasu magungunan zalunci (Lett, 1989, Shippenberg da Heidbreder, 1995, Shippenberg et al., 1996, Vanderschuren da Kalivas, 2000). Tare, wadannan binciken sun nuna cewa halayyar jima'i da martani ga magungunan ƙwayoyi suna yin jarrabawa ta hanyar irin wannan nau'i a cikin tsarin mesolimbic. Saboda haka, haƙiƙa na farko na binciken yanzu shine bincika yadda ake aiwatar da tsarin mesolimbic ta hanyar halayyar jima'i da kuma miyagun ƙwayoyi a cikin wannan dabba. Musamman ma, mun gwada zaton cewa psychostimulant, methamphetamine (Meth), yana aiki ne a kan ƙananan hanyoyi wanda ke daidaita al'amuran jima'i.

Meth yana daya daga cikin magungunan marasa amfani da aka fizguna a duniya (NIDA, 2006, Ellkashef et al., 2008) da kumaan haɗu da shi akai-akai da musanya jima'i. Abin sha'awa, masu amfani da Meth sun nuna sha'awar jima'i da haɓaka, da kuma jin dadin sha'awar jima'i (Semple et al., 2002, Schilder et al., 2005). Bugu da ƙari, Raunin Meth yana hade da halayyar jima'i (Rawson et al., 2002). Masu amfani sukan bayar da rahoto da yawa masu yin jima'i kuma suna iya yin amfani da kariya fiye da sauran magungunan miyagun ƙwayoyi (Somlai et al., 2003, Springer et al., 2007). Abin takaici, binciken da ake nuna Meth yin amfani da shi a matsayin mai hangen nesa na halayen haɗarin jima'i yana iyakance ne kamar yadda suke dogara ga rahotanni marasa tabbaci (Elifson et al., 2006). Sabili da haka, bincike kan tsarin salula na tsarin gyaran Meth wanda ya haifar da halayen jima'i a cikin samfurin dabba yana buƙatar don fahimtar wannan jima'i mai rikitarwa.

Bisa la'akari da shaidun da aka ambata a sama da ke nuna cewa magungunan zalunci, musamman Meth, na iya yin aiki a kan ƙananan hanyoyi wanda ke da alaka da labarun jima'i, makasudin binciken yanzu shi ne bincika aikin haɓaka ta jiki ta hanyar halayyar jima'i da kuma kula da Meth.. Wannan binciken ya aiwatar da hanyar neuroanatomical, ta hanyar yin amfani da samfurin immunohistochemical na farkon jinsin halittar Fos da phosphorylated Map Kinase (PERK) don gano halin da ake ciki na yau da kullum ta hanyar jima'i da Meth. Fos kawai aka bayyana a cikin tsakiya na sel, tare da matsakaicin matakin maganganu na 30-90 bayan kunna neuron. Akwai cikakkun shaida cewa yin jima'i yana haifar da Fos magana a kwakwalwa (Pfaus da Heeb, 1997, Veening da Coolen, 1998), ciki har da tsarin mesocorticolimbic (Robertson et al., 1991, Balfour et al., 2004). Akwai kuma shaida cewa kwayoyi na zalunci suna haifar da kalma a cikin tsarin mesocorticolimbic (Valjent et al., 2000, Valjent et al., 2004, Valjent et al., 2005). Ya bambanta da bayanin Fos, phosphorylation na ERK wani tsari ne mai ƙarfi kuma yana faruwa ne kawai a lokacin 5-20 bayan kunnawa neuronal. Bayanin bayanan na Fos da PERK sun sanya su saitattun alamar alamar alamar sabuntawar neuronal ta hanyoyi daban-daban guda biyu.

HALKAR KARANTA

batutuwa

Dan ragamar dan Adam na Sprague Dawley (210-225 g) da aka samo daga Laboratories na River Charles (Montreal, QC, Kanada) an saka su biyu a kowane cage a cikin cages na plexiglas. An ajiye ɗakin dabba a cikin 12 / 12 H ta juya hasken haske (hasken wuta a 10.00 h). Abincin da ruwa suna samuwa ad libitum. Duk gwaje-gwajen an yi a farkon rabin rabin lokacin duhu a karkashin haske marar haske. Yarin da aka yi amfani da ita don halayen jima'i sun kasance sunadarai ne a karkashin zurfin cutar (13 mg / kg ketamine da 87 mg / kg xylazine) kuma sun sami wani abu mai sassauki wanda ya ƙunshi 5% estradiol benzoate (EB) da kuma 95% cholesterol. Jima'i mai karɓar jima'i ya haifar da gwaninta (s) na aikin 500 μg a cikin 0.1 ml na 4 na XNUMX h kafin an gwada shi. Dukkan hanyoyin sun yarda da Kwamitin Kula da Dabbobi a Jami'ar Western Ontario da kuma bin ka'idodin Kan Kanada Kan Kayan Kanana.

Dabai na gwaji

Gwaje-gwajen 1 da 2: An ba da jinsi maza (n = 37) tare da mace mai karɓa zuwa haɗuwa guda (E) ko na 30 min, wanda bai taɓa samuwa a cikin ɗakunan gwaji mai tsabta ba (60 × 45 × 50 cm) a cikin sau biyar -unin lokacin gwajin gwajin gwaji, don samun jima'i. A lokacin gabatarwa biyu, dukkanin sigogi na daidaituwa don yin jima'i sun rubuta, ciki har da: ƙarancin lalata (ML; lokaci daga gabatarwar mace har zuwa dutse na farko), latency na intromission (IL; lokaci daga gabatarwar mace har sai dutsen farko da sintarwa na ciki), latency ta jiki (El, lokacin daga farkon intromission zuwa haɗuwa), bayan lokaci na haɓaka (PEI, lokaci daga haɗuwa zuwa ƙaddamarwa na farko), yawan adadin (M), da kuma yawan masu ɓoye (IM)Agmo, 1997). Kowane namiji ya karbi 1 ml / kg kowace rana yin amfani da 0.9% NaCl (saline; sc) 3 a gaban kwana kafin ranar gwaji, don haɓakawa don magancewa da injections. Wata rana kafin ranar gwajin, duk maza suna auren gida. A cikin maza da aka sani, Fos za a iya haifar da su ta hanyar halayen yanayin da ke hade da halayen jima'i (Balfour et al, 2004). Saboda haka, duk lokacin da aka gudanar da gwaje-gwaje na karshe an gudanar da su a cikin gidan gida (kauce wa yanayin da aka sani) don hana haɓakar yanayin da aka shigar da shi a cikin mazajen da ba a kula ba. An rarraba mata a cikin kungiyoyi na gwaji guda takwas waɗanda ba su bambanta a kowane nau'i na jima'i ba a cikin lokuta biyu na jima'i (bayanai ba a nuna) ba. A lokacin jarrabawar ƙarshe, an yarda maza su yi aure a cikin gidan su har sai sun nuna jima'i (jima'i) ko kuma ba su sami abokin auren mata (ba jima'i ba). Dukkan maza da aka haifa sun kasance sun rantsar da minti 60 bayan an fara jima'i don ba da damar yin nazari na Fos-expression. Mace sun sami allurar 4 mg / kg Meth ko 1 ml / kg saline (sc) (n = 4 kowannensu), ko 10 (gwaji 1) ko 15 (gwajin 2) min kafin gabatarwa, domin nazarin phosphorylation da aka yi amfani da miyagun ƙwayoyi na MAP kinase. Yankewa da kuma lokacin kafin cin hanci ya kasance bisa rahoto na baya (Choe et al., 2002, Choe da Wang, 2002, Chen da Chen, 2004, Mizoguchi et al., 2004, Ishikawa et al., 2006). Kungiyoyin sarrafawa sun haɗu da maza waɗanda ba su da juna biyu, amma sun karbi Meth 10 (n = 7) ko 15 (n = 5) min kafin hadaya, ko salin inganci 10 (n = 5) ko 15 (n = 4) min kafin hadayar . Bayan yin hadaya, an yi kwakwalwa don maganin immunohistochemistry.

Gwajin 3: Tun lokacin da aka yi amfani da Meth a gwajin 1 da 2, an yi gwajin ƙarin neuroanatomical don bincika idan halayen jima'i da ƙananan ƙarancin Meth sunyi kwaskwarima dangane da aikin haɓakawa na jiki. An gudanar da wannan binciken a cikin wani nau'i kamar gwaje-gwajen 1 da 2. Duk da haka, a jarrabawar ƙarshe, ƙungiyoyin mated da marasa kungiya (n = 6 kowane) sun karbi 1 MG / kg Meth (sc) 15 min kafin hadaya.

Gwajin 4: Don gwada idan kunnawa na jiki da aka haifar da jima'i da Meth da aka ƙayyade ga Meth, wannan gwajin yayi bincike ko irin alamu na gyaran ƙwayar ƙwayoyin jiki zai iya gani tare da amphetamine psychostimulant (Amph). An gudanar da wannan gwaji a wata hanya kamar gwaje-gwajen 1 da 2. Duk da haka, a gwajin karshe, maza ana gudanar da su ko Amph (5 mg / kg) ko saline (1 mg / kg) (sc) 15 min kafin yanka (n = 5 kowanne). Sarrafa maza da ba su da karɓa sun sami saline ko Amph 15 mintuna kafin zuwan hadaya. An ba da cikakken bayani game da kungiyoyin gwaji da aka yi amfani da su a cikin gwaje-gwajen 1-4 Table 1.

Table 1      

Bayani na ƙungiyoyin gwaji sun haɗa da gwaje-gwajen 1-4.

Shirin Shirin

Ana cinye dabbobi da pentobarbital (270 mg / kg; ip) kuma sun hada su tare da 5 ml na salin da 500 ml 4% paraformaldehyde ya biyo a 0.1 M phosphate buffer (PB). An cire kwakwalwa da kuma gyarawa ga 1 h a dakin da zafin jiki a cikin wannan gyara, sa'an nan kuma a cika shi a 20% sucrose da 0.01% Sodium Azide a 0.1 M PB da kuma adana a 4 ° C. Sassan coronal (35 μm) an yanke a kan microtome mai daskarewa (H400R, Micron, Jamus), wanda aka tattara a cikin jigilar hudu a cikin bayani cryoprotectant (30% sucrose da 30% ethylene glycol a 0.1 M PB) da kuma adana a 20 ° C har sai an cigaba aiki.

Immunohistochemistry

Dukkan abubuwan da aka yi sun kasance a cikin dakin da zazzabi tare da tawali'u. An wanke sassa daban-daban na iyo tare da 0.1 M Phosphate-bufe saline (PBS) tsakanin incubations. An saka sassan a cikin 1% H2O2 don 10 min, sa'an nan kuma an katange shi a bayanin bayani (incarnation) (PBS dauke da 0.1% salubin albumin bovine da 0.4% Triton X-100) don 1 h.

PERK / Fos

An kwantar da mutum a cikin dare tare da wani zubar da kwayar cutar polyclonal a kan p42 da p44 map kinases ERK1 da ERK2 (PERK; 1: gwajin 400 1 19; 1: gwajin 4.000 2 da 3 21; 9101 H incubations tare da IgG anti-rabbit na halitta Ign (1: 1, Jackson Immunoresearch Laboratories, West Grove, PA) da kuma avidin-horseradish peroxidase complex (ABC Elite; 500: 1, Laboratories Vector, Burlingame, CA). Bayan haka, an kwantar da nama don 1000 min tare da tyramide na biotinylated (BT; 10: 1 a PBS + 250% H2O2; Kitar Amfani da Alamar Kirar Kira, NEN Life Sciences, Boston, MA) da 30 min tare da tashar strepavidin conjugated na Alexa 488 (1: 100, Jackson Laboratories Immunoresearch, West Grove, PA). Bayan haka, an kwantar da nama a cikin dare tare da rabbit polyclonal antibody a kan c-Fos (1: 500; SC-52; Santa Cruz Biotechnology, Santa Cruz, CA), kuma daga bisani 30 min tare da kututtukan goat Alexa 555 (1: 200, Jackson Laboratories na Immunoresearch, West Grove, PA). Abubuwan da ke biyo baya, an wanke sassa a cikin 0.1 M PB, an saka su akan gilashin gilashi tare da 0.3% gelatin a ddH20 kuma an rufe shi tare da matsakaiciyar matsakaici (Gelvatol) dauke da wakili na anti-fading 1,4-diazabicyclo (2,2) octane (DABCO; 50 mg / ml, Sigma-Aldrich, St. Louis, MO). Dokokin Immunohistochemical sun hada da sakawa daga ko dai ko duka magunguna guda biyu, wanda ya haifar da rashin yin lakabi a cikin tsayin da ya dace.

data Analysis

Halin jima'i

Ga dukkan gwaje-gwaje guda hudu, an rubuta sigogi na daidaito don yin jima'i kamar yadda aka bayyana a sama kuma an yi nazari ta yin amfani da nazarin bambancin (ANOVA). Bayanin bayanan bayanai game da halayen jima'i a lokacin gwajin gwajin ƙarshe bai nuna bambanci tsakanin kungiyoyi a cikin kowane sigogi na yin jima'i ba.

KASHI / Fos Cell Counts

Kwayoyin guda biyu da dual labeled Fos da PERK an kidaya su a cikin matakan caudal na tsakiya na NAc da harsashi na rukuni, amygdala mai kwakwalwa (BLA), amincin amygdala (MEApd), tsakiyar amygdala (CeA), tsakiya na farko (MPN), postromedial da ƙananan gado na tsakiya na stria terminalis (BNSTpm da BNSTpl), da kuma yanki na baya (ACA), prelimbic (PL), da kuma subregions infralimbic (IL) na mPFC. An kama hotuna ta amfani da kyamarar CCD mai sanyaya (Microfire, Optronics) a haɗe zuwa na'urar microscope Leica (DM500B, Leica Microsystems, Wetzlar, Jamus) da kuma software na Neurolucida (MicroBrightfield Inc) tare da saitunan kyamara masu mahimmanci don duk batutuwa (ta amfani da manufofin 10x). Amfani da software na neurolucida, an tsara wuraren nazarin akan alamun (Swanson, 1998) na musamman ga kowane ɓangaren ƙwaƙwalwa (duba Figure 1). Anyi amfani da wuraren bincike na musamman a duk yankuna sai dai NAc da kuma harsashi. A cikin wurare na ƙarshe, BABI da Fos magana ba su da kama da kuma bayyana a cikin patch-kamar alamu. Saboda haka, dukkanin ginshiƙan da harsashi an tsara su ne bisa ga alamomin (alamar motsa jiki, wasanni na baya, da tsibirin Calleja). Yankunan bincike ba su bambanta tsakanin ƙungiyoyi masu gwaji, kuma sun kasance 1.3 mm2 a cikin NAc da kuma harsashi. Yankunan bincike na sauran wurare sune: 1.6 mm2 a cikin BLA, 2.5 da 2.25 mm2 a cikin MEApd da CeA, 1.0 mm2 a MPN, 1.25 mm2 a cikin subdivisions BNST da mPFC, da 3.15 mm2 a cikin VTA. Sassan biyu an kidaya su a kowane ƙwaƙwalwa ta kowace dabba, da kuma adadin guda biyu da dual labeled Kwayoyin don FARK da Fos da kuma kashi na kwayoyin halitta da aka bayyana Fus marker an ƙidaya su. Don gwaje-gwajen 1, 2, da kuma 4, ana kwatanta adadin adadin ta hanyar amfani da hanyoyi biyu ANOVA (dalilai: mating da miyagun ƙwayoyi) da kuma LSD Fisher bayan hoc kwatanta a wani muhimmin matakin na 0.05. Don 3 gwaji, an kwatanta yawan adadin yawan kuɗaɗɗai ta yin amfani da gwaje-gwaje marasa kyauta a hanyar 0.05 mai muhimmanci.

Figure 1      

Hotuna da zane-zane da ke nuna wuraren kwakwalwa na bincike. Bayanan bincike an nuna sune ne akan alamomi na musamman ga kowane ɓangaren ƙwaƙwalwa, ba ta bambanta tsakanin ƙungiyoyi na gwaji, kuma sun kasance 1.25 mm2 a cikin subregions na mPFC (a), 1.3 mm2 a cikin ...

images

Hotunan hotuna don Figure 3 An kama su ta amfani da kamara CCD (DFC 340FX, Leica) a haɗe zuwa na'urar microscope Leica (DM500B) kuma an shigo da su cikin Adobe Photoshop 9.0 software (Adobe Systems, San Jose, CA). Ba'a canza hotuna a kowane hanya sai dai daidaitawar haske.

Figure 3      

Hotunan wakiltar mazabun NAc sun riga sun yi wa Fos (ja; a, d, g, j) kuma suna kallo (kore; b, e, h, k) na dabbobin kowace gwaji: Babu Jima'i + Sal (a, b, c) , Jima'i + Sal (d, e, f), Babu Jima'i + Meth (g, h, i), da Jima'i + Meth (j, k, l). Ƙungiyoyi na dama suna ...

Sakamakon

Ƙarƙashin Ƙarƙashin Ƙarƙashin Ƙarƙashin Ƙarƙashin Ƙarƙashin Ƙarƙashin Ƙarƙwarar Maɗaukaki da Meth Administration

Gwajin 1: Bincike na kwayoyin halitta guda biyu da dual don samowa Fos da Meth-induced a cikin maza da suka karbi Meth 10 mintoci kafin zuwan hadaya da aka gabatar da Fos a cikin MPN, BNSTpm, NAc da harsashi, BLA, VTA, da kuma dukkanin yankuna na mPFC, daidai da nazarin da suka gabata da ke nuna jigilar Fos magana a wadannan yankuna (Baum da Everitt, 1992, Pfaus da Heeb, 1997, Veening da Coolen, 1998, Hull et al., 1999). Gidan Meth 10 mintoci kafin zuwan sadaukarwa KASHE a cikin NAc da harsashi, BLA, MeApd, CeA, BNSTpl, da yankuna na mPFC, da daidaitattun alamu da wasu magunguna suka haifar (Valjent et al., 2000, Valjent et al., 2004, Valjent et al., 2005).

Bugu da ƙari, an gano alamu guda uku na maganin rikici ta hanyar haɓaka ta hanyar jima'i da Meth: Na farko, an gano wuraren da ke cikin kwakwalwa inda jima'i da magungunan sun yi amfani da ƙananan ƙananan halittu (Table 2). Musamman, a cikin CeA, MEApd, BNSTpl, da mPFC, ƙaruwa mai mahimmanci a cikin duka kwayar da kwayar ta haifar (F (1,16) = 7.39-48.8; p = 0.015- <0.001) da kuma Fos da ke cikin jima'i (F (1,16, 16.53) = 158.83-0.001; p <1,16) an kiyaye. Koyaya, a cikin waɗannan yankuna babu ƙarin ƙaruwa mai mahimmanci a cikin ƙananan ƙwayoyin hannu masu ɗauka a cikin mazan da aka kula da Meth. Iyakar abin da ya keɓance shi ne MEApd, inda aka sami tasirin saduwa a kan lambobi na ƙwayoyin halitta masu biyu (F (9.991) = 0.006; p = XNUMX). Koyaya, babu wani sakamako mai mahimmanci na maganin ƙwayoyi da lakabi biyu a cikin ƙungiyoyin da aka kula da Meth basu da mahimmanci sama da ƙungiyoyin da aka kula dasu, saboda haka ba maganin bane ya haifar (Table 2). Na biyu, an gano wuraren da ke cikin kwakwalwa a inda aka fara aiki ne kawai ta hanyar mating (Table 3). Musamman, an kunna MPN, BNSTpm, da VTA kawai ta hanyar mating, kuma sun ƙunshi ƙananan haɓaka a Fos (F (1,16) = 14.99-248.99; p ≤ 0.001), amma ba Meth-induced PERK.

Table 2      

Bayani na maganganun Fos da Meth da aka samu a cikin mahaukaci HAUSA kalma a wurare masu kwakwalwa inda jima'i da kwayoyi sunyi aiki da ƙananan ƙwayoyin halitta.
Table 3      

Bayani na sharuddan Fos da Meth-induced FERK kalma a wurare masu kwakwalwa inda aka haɓaka aikin ne kawai ta hanyar mating.

Daga ƙarshe, an gano wuraren da aka kwakwalwa inda yarinya da magungunan kwayoyi ke kunna yawan yawan ƙananan matuka (Figure 2 da kuma Da kuma 3) .3). A cikin NAc core da harsashi, BLA, da ACA, akwai tasirin tasirin mating (F (1,16) = 7.87-48.43; p = 0.013- <0.001) da kuma maganin ƙwayoyi (F (1,16) = 6.39– 52.68; p = 0.022- <0.001), kazalika da hulɗa tsakanin waɗannan abubuwan biyu (F (1,16) = 5.082-47.27; p = 0.04- <0.001; babu wata ma'amala mai mahimmanci a cikin ACA) akan lambobin sel da ke bayyana duka shigarwar Fos da Meth ta haifar da matsala. Bayanan bayanan bayanan sun nuna cewa lambobi masu lamba guda biyu da aka yiwa lakabi sun kasance mafi girma a cikin maza masu allurar rigakafin Meth idan aka kwatanta da wanda ba'a kula da shi ba Meth (p = 0.027- <0.001), ko kuma maganin da aka yi wa saline (p = 0.001- <0.001) maza (Figure 2 da kuma Da kuma 3) .3). Lokacin da aka bayyana bayanai a matsayin kashi na maɓuɓɓuka masu amfani da miyagun ƙwayoyi, 39.2 ± 5.3% a cikin NAc, 39.2 ± 5.8% a cikin nauyin NAc, 40.9 ± 6.3% a cikin BLA, da 50.0 ± 5.3% na alamar ACA an kunna ta duka mating da Meth.

Figure 2      

Foshin da ke cikin jima'i da Meth-induced KARA kalma a cikin NAc, BLA, da ACA neurons 10 min bayan gudanarwa na 4 mg / kg Meth. Yawancin lambobi ± sem na Fos (a, d, g, j), pERK (b, e, h, k), da kuma dual (c, f, i, l) a cikin NAC na (a, ...

Sanarwar da ba ta gani ba ce cewa halin jima'i ya shafi Meth-induced PERK. Kodayake Meth ya haifar da matakai a cikin ƙungiyoyi na Meth-injected, da NAc, BLA, da ACA, sun nuna cewa lakabi yana da muhimmanci ƙwarai a cikin namiji da aka haifa Meth-injected idan aka kwatanta da mazaje masu ƙwayoyin Meth wanda ba a ciki ba. (Hoto 2b, e, h, k; p = 0.017- <0.001). Wannan binciken zai iya ƙara tallafawa jimlar cewa jima'i da magungunan magunguna sunyi aiki a kan wannan nau'i, amma kuma yana iya nuna alamomin gyare-gyaren mating a cikin magungunan miyagun ƙwayoyi ko metabolism wanda hakan ya haifar da martani ga Meth. Don bincika idan halayen jima'i ya haifar da wani nau'i na magungunan maganin miyagun ƙwayoyi, sassan NAC, BLA, da ACA sun kasance da tsabta ga maza da aka yanka a wani lokaci na gaba (15 min) bayan gwamnatin miyagun ƙwayoyi (gwajin 2).

Gwajin 2: Tarin kwayoyin halitta da dual labeled sun tabbatar da binciken da aka bayyana a sama cewa halin jima'i da haɗakarwa zuwa Meth 15 mintoci kafin zuwan hadaya ya haifar da ƙara yawan Fos kuma ya kaddara immunolabeling a cikin NAC da harsashi, BLA, da ACA. Bugu da} ari, an sake gano mahimmancin maganganun bayanan Fos da Meth-induced PERK, a cikin wadannan yankunan (Figure 4; sakamako na mating: F (1,12) = 15.93-76.62; p = 0.002- <0.001; sakamakon kwayoyi: F (1,12) = 14.11-54.41; p = 0.003- <0.001). Yawan nau'ikan jijiyoyi guda biyu da aka yiwa lakabi a cikin mazan da aka yiwa allurar rigakafin maza sun kasance mafi girma idan aka kwatanta da na Meth da ba a kula da shi ba (p <0.001) ko kuma wanda aka kula da shi (p <0.001). Lokacin da aka bayyana bayanai a matsayin kaso na ƙananan ƙwayoyin cuta, 47.2 ± 5.4% (NAc core), 42.7 ± 7.6% (NAc shell), 36.7 ± 3.7% (BLA), da 59.5 ± 5.1% (ACA) na ƙananan ƙwayoyin da aka kunna ta hanyar saduwa kuma Meth ya kunna ta. Bugu da ƙari, abubuwan da ke haifar da kwayoyi ba su bambanta tsakanin dabbobin da suka dace da dabbobin da ba su tsufa ba (Hoto 4b, e, h, k), a duk yankuna banda ACA (p <0.001). Wadannan bayanan suna nuna cewa halayyar jima'i lallai tana haifar da canjin yanayin lokaci na shigar da kwazo ta hanyar Meth.

Figure 4      

Foshin da ke cikin jima'i da Meth-induced KARA kalma a cikin NAc, BLA, da ACA neurons 15 min bayan gudanarwa na 4 mg / kg Meth. Yawancin lambobi ± sem na Fos (a, d, g, j), pERK (b, e, h, k), da kuma dual (c, f, i, l) a cikin NAC na (a, ...

Ƙarƙashin Ƙarƙashin Ƙarƙashin Ƙarƙashin Ƙarƙwarar Bayanin Jima'i da 1 MG / kg Meth

Ya zuwa yanzu sakamakon ya nuna cewa halayyar jima'i da 4 MG / kg Meth ya kunna yawan mutanen da ke aiki a cikin nauyin NAC da harsashi, BLA, da ACA. To bincika tasirin maganin maganin miyagun ƙwayoyi a kan wannan farfadowa a kunnawa, ana nazarin sifofin ƙirar ƙwayoyin jiki ta amfani da ƙananan ƙwayar Meth. An kirkiro NAC da harsashi, BLA, da ACA don kunnawa da aka samu ta hanyar jima'i da Meth. Lallai, halayen jima'i da nunawa ga Meth sun haifar da ƙananan Fos kuma sun kaddamar da immunolabeling a cikin ƙungiyar NAc da harsashi, da BLA, da ƙananan haruffa a yankin ACA na mPFC (Figure 5). Abin sha'awa shine, ƙananan ƙwayar Meth ya haifar da lambobi iri guda kamar yadda 4 mg / kg Meth yayi a cikin kwakwalwa hudu. Mafi mahimmanci, nauyin NAC da harsashi, BLA, da ACA sun nuna yawan karuwar yawan ƙwayoyin dual labeled (Hoto 5c, f, i, l) idan aka kwatanta da maza da ba a taɓa allura ba (p = 0.003- <0.001). Lokacin da aka bayyana bayanai a matsayin kaso na ƙananan ƙwayoyin cuta, 21.1 ± 0.9% da 20.4 ± 1.8% a cikin NAc core da harsashi bi da bi, 41.9 ± 3.9% a cikin BLA, kuma 49.8 ± 0.8% na ƙananan ƙwayoyin ACA an kunna ta hanyar jima'i da Meth.

Figure 5      

Foshin da ke cikin jima'i da Meth-induced KARA kalma a cikin NAc, BLA, da ACA neurons 15 min bayan gudanarwa na 1 mg / kg Meth. Yawancin lambobi ± sem na Fos (a, d, g, j), pERK (b, e, h, k), da kuma dual (c, f, i, l) a cikin NAC na (a, ...

Ƙunƙirwar Ƙin Kasuwanci bayan halayyar jima'i da kuma gwamnatin d-Amphetamine

Don gwada ko abubuwan da aka samo a sama sun kasance masu mahimmanci ga Meth, an gudanar da ƙarin gwaji don nazarin jima'i- da kuma ƙarfin ƙaddamar da hanyoyi na Amph. Bincike na kwayoyin halitta guda biyu da dual da aka yi amfani da su don nunawa da Fos sun nuna cewa halayen jima'i da kuma nunawa ga Amph ta haifar da ƙara yawan Fos kuma suna kula da immunolabeling a cikin nauyin NAC da harsashi da kuma BLA (Figure 6; tasirin jima'i: F (1,15) = 7.38-69.71; p = 0.016- <0.001; sakamakon kwayoyi: F (1,15) = 4.70-46.01; p = 0.047- <0.001). Bugu da ƙari, lambobin ƙananan ƙwayoyi masu lakabi guda biyu sun kasance mafi girma a cikin maganin Amph da aka bi da su idan aka kwatanta da amph-wanda ba a taɓa jinsa ba (p = 0.009- <0.001), ko kuma wanda aka yi wa saline (p = 0.015- <0.001) maza (Figure 6c, f, i). Lokacin da aka bayyana bayanai a matsayin kashi na kayan aiki masu amfani da miyagun ƙwayoyi, 25.7 ± 2.8% da 18.0 ± 3.2% a cikin nauyin NAC da kuma harsashi daidai da haka, kuma 31.4 ± 2.0% na nau'in BLA sun kunna ta ta hanyar mating da Amph. Ƙungiyar ACA ta mPFC ta nuna manyan matakan matakan Fos (Mating-induced Fos)Hoto 6j; F (1,15) = 168.51; shafi na <0.001). Koyaya, ba kamar Meth ba, Amph bai haifar da ƙaruwa mai yawa ba a cikin ƙwayoyin cuta masu sa maye a cikin ACA (Hoto 6k) ko lambobin lambobin dual labeled a cikin ACA (Hoto 6l) idan idan aka kwatanta da maza biyu da aka yi da saline-injected.

Figure 6      

Fos da Fuskar Hannuwan Jima'i FAR kalma a cikin na'urori NAc, BLA, da ACA 15 min bayan gudanarwa na 5 mg / kg Amph. Yawancin lambobi ± sem na Fos (a, d, g, j), pERK (b, e, h, k), da kuma dual (c, f, i, l) a cikin NAC na (a, ...

DISCUSSION

Binciken na yanzu ya nuna a wani matakin salon salula wanda ya haɓaka tsakanin haɓakawa ta jiki ta hanyar halayyar jima'i na halitta da kuma Meth. Saboda haka, wadannan bayanan sun nuna cewa ba kawai yin amfani da kwayoyi ba ne a cikin sassan kwakwalwa guda daya wanda ke tsara sakamakon lada, amma a gaskiya ma, kwayoyi suna kunna ɗayan Kwayoyin da ke cikin ka'idar dabi'a. Musamman, an nuna a nan cewa halin jima'i da Meth sun taimakawa yawan yawan igiyoyi a cikin yankin na NAC da harsashi, BLA, da ACA na mPFC, gano wuraren da Meth zai iya rinjayar halayen jima'i.

Sakamakon halin yanzu cewa dabi'un jima'i da gudanar da aikin Meth da ke kunshe da yawancin igiyoyi a cikin NAc, BLA, da ACA sun bambanta da binciken daga wasu nazarin da ke nuna cewa yawancin al'ummomin na NAc sun hada da miyagun ƙwayoyi da lada.

Musamman, binciken ilimin electrophysiological idan aka kwatanta da noma a cikin jiki a lokacin sarrafa kansa na abinci (ruwan abinci da ruwa) da kuma cocaine mai ciki sun nuna cewa gwamnatin kai-tsaye ta kunna wani bambanci, yawancin masu amfani da launi wanda ba a karɓa ba a yayin da ake aiki da ruwa da kuma ƙarfin abinci (92%). Nikan 8% na jigilar kayayyaki ya nuna kunnawa ta hanyar cocaine da ladabi na asali (Carelli et al., 2000).

Ya bambanta, mafi rinjaye (65%) na tantanin halitta a cikin NAc ya nuna kunnawa ta hanyar bambance-bambance daban-daban (abincin da ruwa), koda kuwa wani mai karfafawa ya fi dacewa (sucrose) (Roop et al., 2002).

Da dama dalilai na iya taimakawa wajen sabawa da sakamakon yanzu. Na farko, an yi amfani da hanyoyin fasaha daban-daban don gudanar da bincike game da ayyukan da ke cikin gida. Nazarin na yanzu yana amfani da hanyar neuroanatomical don ganowa ta hanyar kunnawa ta jiki ta hanyoyi daban-daban ta hanyar amfani da kwayoyin immunocytochemisty na biyu don Fos da kuma ba da izini, don ƙaddamar da ƙwayar tantancewar kwayar halitta a kan manyan sassan kwakwalwa. Ya bambanta, karatun da Carelli da masu haɗin gwiwar suka yi amfani da rikodin electrophysiological ƙuntatawa ga NAC na nuna halin dabbobi don magance ko yin amfani da kwayoyi masu amfani da kwayoyi da ake amfani da su ta hanyar yin amfani da ma'anar da ke tattare da dabi'a.

Na biyu, nazarin na yanzu ya binciki wani nau'in halitta na daban wanda ya hada da jima'i idan aka kwatanta da binciken da ya gabata, wanda ya yi amfani da abinci da ruwa a cikin ƙuntataccen berayen (Carelli, 2000). Abincin da ruwa na iya samun darajar kuɗi fiye da yadda ake yi. Halin jima'i yana da lada mai yawa kuma ratsaye suna samar da CPP don yin jituwa (Agmo da Berenfeld, 1990, Martinez da Paredes, 2001, Tenk, 2008). Kodayake, rage cin abinci ya hana ratsi suyi CPP don ruwa (Agmo et al., 1993, Perks da Clifton, 1997) da abinci (Perks da Clifton, 1997), dIrin ratsan da ba a raguwa ba zai iya cin abinci da kuma samar da CPP don karin abinci mai mahimmanci (Jarosz et al., 2006, Jarosz et al., 2007).

Na uku, bincikenmu ya haɗa da magunguna daban-daban idan aka kwatanta da binciken da suka gabata, amfani da methamphetamine da amphetamine maimakon cocaine. Sakamakon da ke ciki yanzu ya nuna cewa Meth, da kuma amphetamine mafi ƙarancin, ya sa aka fara aiki da neurons kuma ya kunshi halin jima'i. Harkokin lafiyar kwayar cutar sun iya taka muhimmiyar rawa a bincikenmu. A halin yanzu nazarin amfani da dabbobi da suke da jima'i, amma miyagun ƙwayoyi. Sabanin haka, binciken na electrophysiological na Carelli da masu haɗin gwiwar sunyi amfani da dabbobi "da aka horar da su" da suka karbi lambobin maganin cocaine.

Saboda haka, yana yiwuwa yiwuwar Meth da aka shigar da ƙwayoyin da aka yi ta hanyar halayen jima'i yana canzawa a cikin ƙwayoyi masu fama da kwayoyi. Duk da haka, binciken farko daga jaridarmu ya nuna cewa kwarewar miyagun ƙwayoyi ba zai yiwu ya zama babban mahimmanci kamar yadda halayyar jima'i da gyaran Meth da maza sukayi tare da Meth tare da yin amfani da nau'ikan maganganu masu amfani da miyagun ƙwayoyi kamar yadda aka ruwaito a cikin binciken yanzu (20.3 ± 2.5% a cikin NAc da kuma 27.8 ± 1.3% a cikin NAc; Frohmader da Coolen, wadanda ba a buga su ba).

A ƙarshe, binciken na yanzu ya bincika aikin "kai tsaye" na magungunan amfani da kundin kisa. Sabili da haka, bincike na yanzu bai bayyana bayanin game da hanyoyin da ke tattare da magungunan ƙwayoyi da ke da alaka da ladaran magani ba, amma ya bayyana ayyukan da ke cikin kwayar cutar ta hanyar maganin magungunan magani na miyagun ƙwayoyi. A cikin binciken ilimin kimiyya na baya-bayan nan, aikin NAC wanda ke faruwa a cikin sakanni na amsoshin ƙarfafa ba sakamakon sakamakon aikin maganin cocaine ba, amma yana dogara sosai akan abubuwan haɗin gwiwa a cikin tsarin mulkin kai (Carelli, 2000, Carelli, 2002). Musamman, aikin NAc neural yana rinjayar da gabatarwa mai zaman kanta na samfurori da ke tattare da isar da kwakwalwa na kwakwalwa tare da magungunan kayan aiki (watau maɓallin saɓo) wanda ke tattare a cikin wannan yanayin (Carelli, 2000, Carelli da Ijames, 2001, Carelli, 2002, Carelli da Wightman, 2004). A taƙaice, bincikenmu game da kunnawa ta hanyar sakamako na halitta da miyagun ƙwayoyi na iya kasancewa musamman don kunnawa ta hanyar jima'i da kuma Meth da Amph da aka gudanar.

Meth da jima'i da aka kunna yawan mutanen da ke amfani da su a cikin nauyin NAC da kuma harsashi a cikin hanyar da suka dogara da kashi-kashi. Aikin da aka kunna a cikin NAc na iya magance yiwuwar Meth a kan dalili da kyawawan dabi'un halayen jima'i kamar yadda raunin NAC suka rushe halayen jima'i (Liu et al., 1998, Kippin et al., 2004). Bugu da ƙari, waɗannan ƙwayoyin suna iya samun wuri don maganin ƙwayar magani a kan mating, tun da ƙananan ƙwayoyin Meth (1 mg / kg) sun rage adadin ƙwayoyin dual labeled by 50% idan aka kwatanta da kashi mafi girma na Meth (4 mg / kg). Ko da yake wannan binciken ba ya gano sinadarai sunadarai na ƙananan haɗin gwiwar haɗin gwiwa, binciken da ya gabata ya nuna cewa maganin maganin kwayoyi da kuma Fos expression a cikin NAC dogara ne akan dukkan kwayoyin dopamine (DA) da masu karɓa na glutamate (Valjent et al., 2000, Ferguson et al., 2003, Valjent et al., 2005, Sun et al., 2008). Kodayake ba a bayyana ba idan an kunna nauyin ƙwayoyin jiki a cikin NAc dogara akan waɗannan masu karɓa, an nuna wannan a wasu yankuna na kwakwalwa, musamman ma a cikin yankin na tsakiya (preoptic area)Lumley da Hull, 1999, Dominguez et al., 2007). THussain, Meth yana iya yin aiki a kan igiyoyi kuma an kunna a yayin halayen jima'i ta hanyar kunna dopamine da masu karɓa na glutamate. Matsayi na NAc glutamate a cikin halayen jima'i a halin yanzu ba a sani ba, amma an tabbatar da cewa DA taka muhimmiyar rawa a cikin dalili don halin jima'i (Hull et al., 2002, Hull et al., 2004, Pfaus, 2009). Nazarin Microdialysis ya ruwaito cewa ƙãra ta NAC DA efflux a lokacin da ake amfani da shi da kuma halayen maza da mata na hali (Fiorino da Phillips, 1999a, Lorrain et al., 1999) da kuma mesolimbic DA efflux an haɗu da su don haɓakawa na farawa da kuma kiyaye nau'in halayen hauka (Pfaus da Everitt, 1995). Bugu da ƙari kuma, nazarin mance-gwaje na DA ya nuna DA masu adawa a cikin NAc sun hana halayyar jima'i, yayin da magunguna suke taimakawa wajen fara halayyar jima'ir (Everitt et al., 1989, Pfaus da Phillips, 1989). Ta haka ne, Meth zai iya shafar motsa jiki don yin jima'i ta hanyar kunnawa DA masu karɓa.

Ya bambanta da NAc, adadin ƙwayoyin dual labeled a cikin BLA da ACA sun kasance ba su canzawa ba tare da la'akari da Meth ba. BLA yana da mahimmanci ga ilmantarwa na haɗin kai da kuma yana da karfi cikin ƙarfafawa da kuma ladaftawa a yayin da ake aiki da kayan aiki (Everitt et al., 1999, Cardinal et al., 2002, Duba, 2002). BLA laioned berayen nuni nuna rage lever latsa don yanayin damuwa hade tare da abinci (Everitt et al., 1989) ko ƙarfafa zuciya (Everitt et al., 1989, Everitt, 1990). Ya bambanta, wannan magudi ba zai shafar lokaci na ciyarwa da halayyar jima'i ba (Cardinal et al., 2002). BLA kuma tana taka muhimmiyar rawa a cikin ƙwaƙwalwar ajiyar yanayin da ke tattare da maganin miyagun kwayoyi (Grace da Rosenkranz, 2002, Laviolette da Grace, 2006). Kwayoyin ko samfurori na ƙwarewar na BLA toshe kayan saye (Whitelaw et al., 1996) da kuma bayyanawa (Grimm da Duba, 2000) gyaran maganin cocaine mai kwakwalwa, yayin da bai shafi tsarin gwamnati ba. Bugu da ƙari, Ƙararrawa ta kunshi kai tsaye a cikin sakamakon BLA a cikin sake dawowa da miyagun ƙwayoyi a cikin gaban kwakwalwa (Dubi et al., 2003). Saboda haka, yana yiwuwa psychostimulant-haɓaka DA watsa a cikin sakamakon BLA a cikin potentiated tunanin salience da neman (Ledford et al., 2003) na lalata jima'i, don haka yana taimakawa wajen bunkasa jima'i da kuma sha'awar da 'yan tawayen Meth ya ruwaito (Semple et al., 2002, Green da Halkitis, 2006).

A cikin ACA, yin amfani da ƙananan jigilar jigilar jima'i yana kasancewa mai zaman kanta da kuma takamaiman Meth, saboda ba a lura da shi ba tare da Amph. Kodayake Meth da Amph suna da irin wannan tsari da kuma kimar kantin magani, Meth ya kasance mai haɗariyar psychostimulant fiye da Amph tare da ciwo mai dorewa (NIDA, 2006). Nazarin da Goodwin et al. ya nuna cewa Meth yana haifar da mafi girma DA efflux da inhibits da yarda na gida amfani DA mafi yadda ya kamata a cikin bera NAc fiye da Amph. Wadannan halaye zasu iya taimakawa wajen haɓaka abubuwa na Meth idan aka kwatanta da Amph (Goodwin et al., 2009) kuma watakila bambance-bambance da ke kunshe da ƙananan ƙwayoyin da ke tsakanin kwayoyi biyu. Duk da haka, ba a fili ba ko siffofin daban-daban na sakamakon sakamakon sabani ne na mahimmanci tsakanin kwayoyi ko al'amurran da suka shafi aiki da suka shafi asibiti da ake aiki kuma ana buƙatar ƙarin bincike.

Ƙungiyar hadin gwiwa ta Meth da jima'i ba a kiyaye shi a wasu ƙananan hukumomi na mPFC (IL da PL) ba. A cikin bera, an yi nazarin ACA da yawa ta hanyar amfani da ayyuka masu gogewa, suna taimakawa wajen raya ƙungiyoyi masu ƙarfafawa (Everitt et al., 1999, Duba, 2002, Cardinal et al., 2003). Akwai shaidun shaida da yawa cewa MPFC yana cikin haɗarin miyagun ƙwayoyi da kuma sake dawowa zuwa neman magani da kuma daukar nauyin miyagun kwayoyi a cikin mutane da berayen (Grant et al., 1996, Childress et al., 1999, Capriles et al., 2003, McLaughlin da Duba, 2003, Shaham et al., 2003, Kalivas da Volkow, 2005). Nin line tare da wannan, an bayar da shawarar cewa dysfunctioning mPFC ta hanyar nunawa sau da yawa zuwa magunguna na zagi iya zama alhakin rage kula da motsa jiki da kuma ƙara yawan shiryarwa da miyagun ƙwayoyi kamar yadda aka lura a yawancin addicts (Jentsch da Taylor, 1999). Bayanan kwanan nan daga dakin gwaje-gwajenmu sun nuna cewa raunin mPFC zai haifar da ci gaba da neman halayen jima'i lokacin da wannan ya haɗu da wani abu mai tasowa. (Davis et al., 2003). Ko da yake wannan binciken bai bincika ACA ba, yana tallafawa ra'ayin cewa MPFC (da ACA musamman) sunyi tasiri game da sakamakon Meth a kan asarar iko akan hana jima'i kamar yadda rahoton Meth ya sabawa (Salo et al., 2007).

A ƙarshe, tare da waɗannan nazarin sune matakan farko don fahimtar yadda ake amfani da magungunan ƙwayoyin hanyoyi na hanyoyi wanda ke daidaita al'amuran dabi'a. Bugu da ƙari, waɗannan binciken sun nuna cewa a bambanta da gaskiyar yanzu cewa ƙwayoyi na zalunci ba sa kunna nau'ikan kwayoyin halitta a cikin tsarin mesolimbic a matsayin sakamako na halitta, Meth, kuma zuwa karamin ƙarami, kunna ɗayan Sannan kamar yadda zinare. Hakanan, waɗannan ƙananan ƙananan hanyoyi suna iya rinjayar neman dabi'ar dabi'a bayan bayyanar miyagun ƙwayoyi. A ƙarshe, sakamakon wannan binciken zai iya taimakawa sosai ga fahimtarmu game da jaraba a gaba ɗaya. Daidaitawar kamance da bambance-bambance, da gyare-gyare a cikin kunnawa na tsarin mesolimbic wanda aka haifar da halayyar jima'i tare da magungunan zalunci zai iya haifar da kyakkyawan fahimtar cin zarafin abubuwa da kuma haɓaka canji a cikin ladabi.

Acknowledgments

Wannan bincike ya goyi bayan tallafi daga Cibiyar Kula da Lafiya ta R01 DA014591 da Cibiyar Nazarin Lafiya ta RN 014705 na Kanada zuwa LMC.

ABBREVIATIONS

  • ABC
  • avidin-biotin-horseradish peroxidase hadaddun
  • ACA
  • Yankin shinge na baya
  • Ƙarfi
  • d-amphetamine
  • BLA
  • amygdala basalt
  • BNSTpl
  • matsakaicin gado na tsakiya na stria terminalis
  • BNSTpm
  • matsakaicin gado mai kwakwalwa na stria terminalis
  • BT
  • biotinylated tyramide
  • CeA
  • tsakiya amygdala
  • CPP
  • Yanayin da aka sanya dashi
  • E
  • ejaculation
  • EL
  • latency tajaci
  • IF
  • yankin infralimbic
  • IL
  • latency intromission
  • IM
  • intromission
  • M
  • Dutsen
  • MAP Kinase
  • haɓakar kinase mai kunnawa ta jiki
  • MEApd
  • amygdala dan wasan tsakiya
  • Meth
  • methamphetamine
  • ML
  • Rashin ikon lalata
  • mPFC
  • matsala na farko a cikin kwakwalwa
  • MPN
  • tsakiya na preoptic
  • NAc
  • Accumbens
  • PB
  • phosphate buffer
  • PBS
  • phosphate buffered saline
  • PEI
  • matsayi na baya-lokaci
  • KAI
  • phosphorylated MAP Kinase
  • PL
  • prelimbic yankin
  • VTA
  • ƙananan yanki na yanki

Bayanan kalmomi

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