Amphetamine imasintha khalidwe ndi mesocorticolimbic dopamine receptor mawu mu mzimayi wam'madzi yekha (2011)

Resin ya ubongo. Zolemba zolemba; ilipo mu PMC Jul 25, 2011.

Lofalitsidwa mu mawonekedwe omaliza omaliza monga:

Resin ya ubongo. Jan 7, 2011; 1367: 213-222.

Yofalitsidwa pa intaneti pa Okutobala 8, 2010. doi: 10.1016/j.brainres.2010.09.109

PMCID: PMC3143067

NIHMSID: NIHMS312646

Nkhani yomaliza yosinthidwa ndi wofalitsa ikupezeka pa Brain Res

Onani nkhani zina mu PMC zomwe zikufotokoza nkhani yofalitsidwayi.

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Kudalirika

Posachedwapa takhazikitsa njira yodziwira momwe dopamine ( DA ) imakhudzira anthu omwe ali ndi vuto la amphetamine (AMPH) imakhudzira khalidwe la anthu. Popeza ntchito yathu yambiri, mpaka pano, yayang'ana kwambiri amuna, ndipo kusiyana kwa amuna ndi akazi kumafotokozedwa kawirikawiri m'mayankho a khalidwe ndi mitsempha ku AMPH, kafukufuku wapano adapangidwa kuti afufuze zotsatira za khalidwe ndi mitsempha za chithandizo cha AMPH m'ma voles achikazi a ku prairie. Tinagwiritsa ntchito njira yodziwira momwe munthu amakhudzira khalidwe lake (CPP) kuti tidziwe momwe munthu amakhudzira khalidwe lake (CPP) m'ma voles achikazi a ku prairie, ndipo tinapeza kuti njira yodziwira momwe munthu amakhudzira thupi lake (0.2 ndi 1.0 mg/kg) imakhudzira thupi lake, koma osati yotsika kwambiri (0.1 mg/kg), ya AMPH inachititsa kuti munthu akhale ndi CPP. Tinapezanso kuti kupezeka ndi mlingo wofunikira wa AMPH (1.0 mg/kg) kunapangitsa kuti kuchuluka kwa DA mu nucleus accumbens (NAcc) ndi caudate putamen kuchuluke koma osati medial prefrontal cortex kapena ventral tegmental area (VTA). Pomaliza, kupezeka mobwerezabwereza kwa AMPH (1.0 mg/kg kamodzi patsiku kwa masiku atatu otsatizana; njira yojambulira yomwe yawonetsedwa posachedwa kuti imasintha mawonekedwe a DA receptor ndikusokoneza mgwirizano wa anthu m'magulu a amuna aku prairie voles) kunawonjezera D1, koma osati D2, receptor mRNA mu NAcc, ndikuchepetsa D2 receptor mRNA ndi D2-like receptor binding mu VTA. Pamodzi, deta iyi ikuwonetsa kuti AMPH imasintha mesocorticolimbic DA neurotransmission mwanjira yachigawo ndi receptor, zomwe, zimatha kukhala ndi zotsatirapo zazikulu pa khalidwe la anthu m'magulu a akazi aku prairie voles.

Keywords: Psychostimulant, Nucleus accumbens, Veteral tegmental dera, Autoreceptor, Pair bonding, Malo okonzedwa m'malo

1. Introduction

Kugwiritsa ntchito mankhwala osokoneza bongo akuganiza kuti akuwongolera mphamvu zawo pazochita zawo, mbali imodzi, mwa zotsatira zake pa ma mesocorticolimbic dopamine (DA)Kelley ndi Berridge, 2002; Nesse ndi Berridge, 1997; Nestler, 2004, 2005; Panksepp et al., 2002), dera la neural lomwe liri ndi maselo opanga DA omwe amachokera ku ventral tegmental area (VTA) ndi polojekiti ku madera osiyanasiyana, kuphatikizapo medieval prefrontal cortex (PFC) ndi nucleus accumbens (NAcc). Msewu wotetezedwa kwambiri wa neural, womwe umakhala ndi gawo lofunika kwambiri m'kukhala ndi zolinga zogwirizana ndi cholinga (Zahm, 2000) - kuphatikizapo makhalidwe omwe amapezeka kwa zinyama zonse (mwachitsanzo, kudyetsa (Narayanan et al., 2010; Palmiter, 2007)) ndi zomwe zili zamoyo (mwachitsanzo, zibwenzi zomwe zimagwirizana ndi mitundu ina (Aragona ndi Wang, 2009; Curtis et al., 2006; Young et al., 2010)) - amasinthidwa kwambiri powonetsa mankhwala osokoneza bongo. Mwachitsanzo, kuwonetsa koopsa komanso / kapena mobwerezabwereza ku mankhwala osokoneza bongo, monga cocaine kapena amphetamine (AMPH), kumabweretsa kusintha kwa DA, kutulutsa mawu kwa DA komanso kutsimikizika, komanso chiphunzitso cha neuronal morphology mkati mwa mesocorticolimbic zigawo za ubongo (Henry et al., 1989; Henry ndi White, 1995; Hu et al., 2002; Nestler, 2005; Pierce ndi Kalivas, 1997; Robinson et al., 2001, 1988; Robinson ndi Kolb, 1997; White ndi Kalivas, 1998). Zikuganiziridwa kuti mapuloteniwa amatha kusintha kusintha kwa mankhwala mwa chikhalidwe cha nyama (Robinson ndi Becker, 1986), kuphatikizapo makhalidwe abwino (kuti awonenso, onani (Young et al., 2011)).

Ntchito yaposachedwa kuchokera ku labotayi yakhazikitsa malo odyetserako ziweto monga zitsanzo za zinyama kuti afufuze kugawana kwa mesocorticolimbic DA mu zotsatira za mankhwala osokoneza bongo pa chikhalidwe cha anthu (Liu et al., 2010). Mapiri a prairie ndi makoswe amodzi omwe amapanga makondomu omwe amapanga zokondweretsa mnzawo yemwe amadziwika bwino (mwachitsanzo, kukonda mnzanu) pambuyo poti azikhala pamodzi komanso /Insel et al., 1995; Williams et al., 1992; Winslow et al., 1993), ndi mesocorticolimbic DA - makamaka DA neurotransmission mu NAcc - ndi yofunikira pa njira iyi (Aragona et al., 2003, 2006; Aragona ndi Wang, 2009; Curtis et al., 2006; Gingrich et al., 2000; Liu ndi Wang, 2003; Wang et al., 1999; Young et al., 2010). Chochititsa chidwi, kuwonetsedwa kwa AMPH kumasintha kwambiri ntchito ya mesocorticolimbic DA ndi njira yothandizira anthu m'mimba yamwamuna. Mwachitsanzo, jekeseni imodzi ya AMPH yowonjezera kuchuluka kwa DA solcellular levels mu NAcc (Curtis ndi Wang, 2007). Kuonjezera apo, masiku atatu a AMPH, omwe amachititsa kuti mapangidwe a malo apangidwe (CPP) apangidwe ngati ali ndi malo ozungulira chilengedwe, adasintha mawu a DA receptor ku NAcc mwachindunji (Liu et al., 2010). Chofunika kwambiri, mankhwala omwewa amaletsa kupanga mapangidwe a okondedwa omwe akugonana nawo, kusonyeza kuti kusintha kwa AMPH kwa mesocorticolimbic DA kutsegula kwadzidzidzi kungayambitse kufooka kwa AMPH-kuchititsa kuti pakhale kugwirizana pakati pa mitundu iyi (Liu et al., 2010).

Ngakhale kuti maphunziro omwe tatchulidwa pamwambapa adakhazikitsa phokoso lachitsanzo ngati chitsanzo chabwino kwambiri choyenera kuyesa kuwonongeka kwa AMPH komwe kunayambitsa kugwirizana kwa anthu komanso njira zake zoyendetsera mitsempha, zinkachitidwa mwa amuna okha. Chifukwa chake, sitikudziwa pang'ono za zotsatira za khalidwe ndi zokhudzana ndi matenda a AMPH muzimayi za prairie. Umboni ulipo wosonyeza kuti mbalame zam'madzi zimakonda kwambiri AMPH kuposa mbalame zam'mimba (Aragona et al., 2007) komanso kafukufuku wa mitundu ina yambiri imanena za kusiyana pakati pa kugonana ndi zotsatira za khalidwe ndi matenda a AMPH komanso mankhwala ena ozunguza bongo (psychostimulant)Becker ndi Hu, 2008; Fattore et al., 2008; Lynch, 2006). Mwachitsanzo, makoswe aakazi amasonyeza ntchito zowonjezera zazikulu komanso kuwonjezereka kofulumira kwa khalidwe poyankha AMPH (Camp ndi Robinson, 1988), pitani cocaine ndi methamphetamine kudzipangira mofulumira (Hu et al., 2004; Lynch, 2006; Lynch ndi Carroll, 1999; Roth ndi Carroll, 2004), ndikuwonetseratu zowonjezera zowonjezera kupeza psychostimulants (Roberts ndi al., 1989; Roth ndi Carroll, 2004) kuposa amuna. Kuwonjezera apo, kusiyana kwa kugonana kwapezeka mu njira yokhudzana ndi kugonana kwa psychostimulants, kuphatikizapo kusiyana kwa AMPH-inachititsa DA kumasulidwa (Becker, 1990; Becker ndi Ramirez, 1981), Metabolism ya DA (Camp ndi Robinson, 1988), ndi posachedwa kufalitsa ma gene (Wopereka ndi Becker, 1996). Kupenda zotsatira za ubongo wa AMPH m'madera a prairie voles ndizofunikira kwambiri kukhazikitsa njira yophunzirira za kugonana pakati pa mankhwala osokoneza bongo, chikhalidwe cha anthu, ndi mesocorticolimbic DA.

Kafukufuku wapano adapangidwa kuti afufuze zotsatira za machitidwe ndi mitsempha ya AMPH m'malo opezeka akazi. Tinagwiritsa ntchito njira ya CPP yomwe idakhazikitsidwa kale m'malo opezeka amuna ( Liu et al., 2010 ) kuti tiwone kufunika kwa machitidwe osiyanasiyana a AMPH mwa akazi. Popeza akazi amakonda kuwonetsa kukhudzidwa kwakukulu kwa khalidwe la AMPH kuposa amuna ( Aragona et al., 2007 ; Becker et al., 2001 ; Camp ndi Robinson, 1988 ), tinaganiza kuti malo opezeka akazi a prairie angapange CPP pamlingo wochepa wa AMPH kuposa womwe unanenedwa kwa amuna. Tinafufuzanso zotsatira za kupezeka kwa AMPH pa kuchuluka kwa DA ndi DA receptor gene ndi kumangirira m'madera osiyanasiyana a ubongo wa mesocorticolimbic. Tinaganiza kuti kupezeka kwa AMPH kungasinthe kuchuluka kwa DA ndi DA receptor expression mwanjira ya receptor- ndi chigawo. Zotsatira za kafukufuku wapano zipereka chidziwitso chothandiza pantchito yamtsogolo yomwe imayang'ana zotsatira za AMPH pa khalidwe la anthu mwa akazi amtunduwu.

2. Zotsatira

2.1. Yesetsani 1: AMPH kukhazikitsa CPP

Kuyesera koyamba kunakhazikitsa njira yoyezera mlingo wa CPP yomwe imachokera ku AMPH m'ma voles achikazi a ku prairie. Kuti tiyerekezere njira yoyezera mlingo wa azimayi ndi amuna, tinagwiritsa ntchito njira yoyezera yofanana ndi yomwe idapangidwa posachedwapa m'ma voles achimuna a ku prairie ( Liu et al., 2010 ). Anthu adagawidwa mwachisawawa m'gulu limodzi mwa magulu anayi oyesera omwe adasiyanitsidwa ndi kuchuluka kwa AMPH [0.0 ( n = 20), 0.1 ( n = 8), 0.2 ( n = 12), kapena 1.0 mg/kg ( n = 13)] omwe adalandira panthawi ya AMPH conditioning sessions (onani njira zoyesera kuti mudziwe zambiri). Anthu onse adayesedwa kuti awone ngati CPP ilibe mankhwala tsiku lotsatira nthawi yomaliza conditioning sessions. CPP idafotokozedwa ndi kuwonjezeka kwakukulu kwa nthawi yomwe idagwiritsidwa ntchito mu khola lolumikizidwa ndi mankhwala panthawi yoyesa pambuyo poyerekeza ndi mayeso asanayambe.

Anthu omwe adalandira chithandizo cha saline yokha [0.0 mg/kg; t (19) =1.65; p <0.12] kapena saline yokhala ndi [0.1 mg/kg yotsika kwambiri; t (7) =1.89; p <0.90] kuchuluka kwa AMPH kunathera nthawi yofanana mu chipinda cholumikizidwa ndi mankhwala asanayambe komanso atachira ndipo, motero, sanapange CPP ( Chithunzi 1A ). M'malo mwake, anthu omwe adalandira chithandizo cha 0.2 [t (11) =2.77; p <0.02] kapena 1.0 mg/kg [t (12) =2.53; p <0.03] AMPH inawonetsa CPP yolimba, chifukwa adakhala nthawi yochulukirapo mu chipinda cholumikizidwa ndi mankhwala panthawi yoyesedwa kuposa mayeso asanayambe ( Chithunzi 1A ). Palibe kusiyana kwa ntchito ya locomotor komwe kunawonedwa mkati kapena pakati pa magulu asanayambe kapena atalandira chithandizo cha mankhwala ( Chithunzi 1B ).

Chith. 1 

Amphetamine (AMPH) -dakhala ndi malo okondweretsa malo (CPP) ndi ntchito zogwirira ntchito kuzimayi zachikazi. Amuna omwe analandira 0.0 (saline yekha) kapena 0.1 mg / kg AMPH pa masiku 3 a chikhalidwe sanakhazikitse CPP, chifukwa iwo ankakhala ndi nthawi yofanana ...

2.2. Yesetsani 2: Mankhwala a AMPH adasintha maganizo a DA

Kuyesera 2 kunayang'ana momwe chithandizo chimodzi cha AMPH chimakhudzira kuchuluka kwa DA m'malo osankhidwa a ubongo kuphatikizapo PFC, NAcc, caudate putamen (CP) ndi VTA ( Chithunzi 2A ). Anthu omwe adayesedwa adapatsidwa mwachisawawa m'gulu limodzi mwa magulu awiri oyesera omwe adalandira jakisoni imodzi ya ip ya 0.9% saline ( n = 6) kapena 1.0 mg/kg AMPH yosungunuka mu saline ( n = 6). Mlingo uwu unasankhidwa chifukwa unali wokwanira kuyambitsa CPP mwa akazi (Kuyesera 1) ndi amuna a prairie voles ( Aragona et al., 2007 ; Liu et al., 2010 ), zomwe zikusonyeza kufunika kwake kwa khalidwe kwa amuna ndi akazi onse. Anthu onse adaphedwa patatha mphindi 30 jekeseni itachitika, ndipo kuchuluka kwa DA m'minofu yawo yaubongo kunayesedwa pogwiritsa ntchito high performance liquid chromatography yokhala ndi electrochemical detection (HPLC-ECD).

Chith. 2 

Zotsatira za jekeseni imodzi ya AMPH (1 mg / kg) pa DA yomwe imakhala m'madera a ubongo wa mesocorticolimbic. Chizindikiro chokhazikitsidwa ndi malo omwe amapanga mapiritsi oyendetsera cortox (PFC), nucleus accumbens (NAcc), caudate putamen (CP) ndi chimbudzi ...

Chithandizo chimodzi cha AMPH chinasintha kuchuluka kwa DA m'njira yodziwika bwino m'chigawo chilichonse mkati mwa dongosolo la mesocorticolimbic DA ( Chithunzi 2B ). Anthu omwe adalandira chithandizo cha AMPH anali ndi kuchuluka kwakukulu kwa DA mu NAcc [t (10) = 2.06; p <0.03] ndi CP [t (10) = 2.07, p <0.03] kuposa momwe zidalili zowongolera zomwe zidalowetsedwa ndi saline. Komabe, palibe kusiyana kwa magulu komwe kudapezeka mu PFC [t (10) = 0.03; p <0.49] kapena VTA [t (10) = 1.41; p <0.09].

2.3. Zotsatira za 3 ndi 4: kuwonetsedwa kwa AMPH mobwerezabwereza kumasintha mauthenga a DA receptor mRNA ndi kumanga

Mayeso 3 ndi 4 adafufuza zotsatira za chithandizo chobwerezabwereza cha AMPH pa D1 receptor ndi D2 receptor mRNA expression ndi D1-like ndi D2-like receptor binding, motsatana. Mayeso am'mbuyomu m'ma voles a amuna a prairie awonetsa kuti kuwonetsedwa mobwerezabwereza kwa AMPH (1.0 mg/kg kamodzi patsiku kwa masiku atatu otsatizana) kumasintha kwambiri kuwonetsedwa kwa DA receptor mu NAcc maola 24 pambuyo pa jakisoni womaliza ndipo kuti kusinthaku kungayambitse kuwonongeka kwa mgwirizano wa anthu komwe kumabwera chifukwa cha AMPH ( Liu et al., 2010 ). Chifukwa chake, tidagwiritsa ntchito njira iyi yojambulira mankhwala kuti tifufuze zotsatira za mitsempha yamagazi chifukwa cha kuwonetsedwa mobwerezabwereza kwa AMPH mwa akazi. Anthu adagawidwa mwachisawawa m'gulu limodzi mwa magulu awiri omwe adalandira jakisoni wa ip wa saline (control, n = 6) kapena saline yokhala ndi 1.0 mg/kg AMPH ( n = 8), kamodzi patsiku kwa masiku atatu otsatizana. Anthu onse adaperekedwa nsembe maola 24 pambuyo pa jakisoni womaliza. Kuchulukana kwa D1 receptor mRNA ndi D1-like receptor binding kunayesedwa mu NAcc ndi CP pomwe D2 receptor mRNA ndi D2-like receptor binding zinayesedwa mu NAcc, CP ndi VTA. D1R mRNA ndi D1-like receptor binding sizinayesedwe mu VTA chifukwa cha kusowa kwawo m'dera lino la ubongo ( Weiner et al., 1991 ).

Kufotokozera kwa AMPH komweko kunasinthidwa mawu a DA receptor mRNA mu njira yolandira. Mabuku omwe analandira mankhwala a AMPH mobwerezabwereza amasonyeza mlingo wapamwamba kwambiri wa D1 receptor mRNA kulemba mu NAcc [t(12)= 2.85; p <0.01], koma osati CP [t(12)= 1.96; p <0.07], kuposa zowongolera zamchere zamchere (Nkhuyu. 3A ndi B). Palibe kusiyana kwa gulu komwe kunapezeka mu D2 receptor mRNA kulemba mu NAcc [t(12)= 1.56; p <0.14] kapena CP [t(12)= 1.79; p <0.10] (Nkhuyu. 3C ndi D). Komabe, mankhwala omwe amachitidwa mobwerezabwereza amachepetsa kwambiri mlingo wa D2 receptor mRNA mu VTA [t(12)= 3.11; p <0.01] (Nkhuyu. XUMUMI ndi F).

Chith. 3 

Zotsatira za maulendo afupipafupi a AMPH (1 mg / kg / tsiku kwa 3 masiku otsatira) pa dopamine receptor mRNA kulembera m'mimba yaakazi yaikazi. Mankhwala a AMPH owonjezeredwa anawonjezereka mankhwala a D1 receptor (D1R) mRNA kulembera pamtima nucleus accumbens (NAcc), koma osati ...

Kuwonetsedwa kwa AMPH kobwerezabwereza kunalibe mphamvu pa D1-like receptor (Nkhuyu. 4A ndi B) kapena D2-ngati receptor (Nkhuyu. 4C ndi D) kumanga miyezo mu NAcc [D1-ngati: t(12)= 0.40; p <0.35, D2-ngati: t(12)= 0.77; p<0.23] kapena CP [D1-ngati: t(12)= 0.63; p<0.27, D2-ngati: t(12)= 0.91; p<0.19]. Komabe, maphunziro omwe amathandizidwa ndi AMPH anali ndi gawo lotsika kwambiri la D2-ngati receptor yolumikizidwa mu VTA kuposa momwe amathandizira ma jekeseni a saline [t(12)= 1.91; p<0.04] (Nkhuyu. 4E ndi F).

Chith. 4 

Zotsatira za maulendo obwerezabwereza AMPH (1 mg / kg / tsiku kwa 3 masiku otsatira) pa dopamine receptor kumangirira m'mimba ya prairie vole. Mankhwala a AMPH omwe sanabwerezenso sanasinthe D1-ngati (A ndi B) kapena D2-ngati receptor kumanga miyezo (C ndi D) mu ...

3. Kukambirana

Kafukufuku wamakono akufufuzira zotsatira za khalidwe ndi zokhudzana ndi khalidwe la ubongo la AMPH kuzimayi za prairie. Pamodzi, deta yathu ikuwonetsa kuti AMPH ili ndi zotsatira zokhudzana ndi chidziwitso pa khalidwe, imapangitsa kuti DA igwirizane ndi NAcc ndi CP, ndipo imasintha mazenera a DNA ndikumangika pamtundu uliwonse. Deta iyi ikhoza kumapereka chidziwitso chothandiza pa kafukufuku wamtsogolo kuti ayang'ane zotsatira za AMPH mmalo mwa chikhalidwe cha akazi a mitundu iyi.

CPP ikuwonetsa kukonda kwa chilengedwe komwe kwagwirizanitsidwa ndi chowonjezera chachikulu ( Bardo ndi Bevins, 2000 ) - pankhaniyi, AMPH - ndipo nthawi zambiri imagwiritsidwa ntchito ngati muyeso wokhudzana ndi khalidwe, ngakhale wosalunjika, wa mphotho ya mankhwala. Zotsatira zathu zikuwonetsa kuti akazi a prairie voles amapanga CPP pambuyo pa chithandizo chokhala ndi mlingo wochepa mpaka wapakati wa AMPH. Poyerekeza ndi zotsatira zathu zaposachedwa za amuna a prairie voles omwe adapezeka pogwiritsa ntchito njira yomweyo ya CPP ( Liu et al., 2010 ), deta iyi, pamodzi, ikuwonetsa kusintha kwa kumanzere kwa mlingo-mayankho a CPP m'ma prairie voles a akazi. Makamaka, 0.2 mg/kg kapena mlingo wapamwamba wa AMPH unayambitsa CPP mwa akazi, pomwe 1.0 mg/kg kapena mlingo wapamwamba wa AMPH unkafunika kuti CPP ipangidwe mwa amuna ( Liu et al., 2010 ). Kusintha kumeneku kwa kumanzere kwa mlingo ndi mayankho a akazi kukugwirizana ndi kafukufuku wakale m'mabowo a prairie omwe adagwiritsa ntchito njira yosiyana yodziwira momwe zinthu zilili ( Aragona et al., 2007 ), ndipo akuwonetsa kuti akazi amakhala okhudzidwa kwambiri ndi zotsatira za khalidwe, ndipo mwina amakhala pachiwopsezo chachikulu cha zotsatira zabwino, za AMPH kuposa amuna—zomwe zapezeka nthawi zonse m'mitundu ina ( Camp ndi Robinson, 1988 ; Hu et al., 2004 ; Lynch, 2006 ; Lynch ndi Carroll, 1999 ; Roberts et al., 1989 ; Roth ndi Carroll, 2004 ) ndipo zomwe zingakhale ndi tanthauzo lofunikira pa zotsatira za AMPH pa khalidwe la anthu m'mabowo a prairie a akazi.

Mu kafukufuku wapano, tapezanso kuti kupereka AMPH - pa mlingo wogwirizana ndi khalidwe (1.0 mg/kg) kwa akazi a prairie voles - kunawonjezera kuchuluka kwa DA mu NAcc ndi CP koma osati PFC kapena VTA. Zotsatirazi zikusonyeza kuwonjezeka kwa AMPH komwe kumabwera chifukwa cha dera linalake la AMPH. Monga momwe maphunziro am'mbuyomu m'mitundu ingapo adasonyezera kuyambitsa kutulutsidwa kwa DA kunja kwa thupi mu NAcc ndi CP atangolandira jakisoni wa AMPH ( Cho et al., 1999 ; Clausing ndi Bowyer, 1999 ; Curtis ndi Wang, 2007 ; Di Chiara et al., 1993 ; Drevets et al., 2001 ), kuwonjezeka kwa kuchuluka kwa DA m'madera awa mu kafukufukuyu kungakhale chifukwa cha kuwonjezeka kwa AMPH komwe kumabwera chifukwa cha kaphatikizidwe ka DA ndi kagayidwe kake, malingaliro awa ayenera kuyesedwa mu zoyeserera zina. Kuphatikiza apo, panali njira yodziwika bwino yochepetsera kuchuluka kwa DA mu VTA pambuyo pa kuwonetsedwa kwa AMPH m'ma prairie voles achikazi. Ngakhale kuti zotsatira zake sizinali zazikulu ( p < 0.09), kuyeserera kwina kumafunika kuti kudziwike kapena kuchotsa zotsatira za AMPH pa kuchuluka kwa DA m'dera lino la ubongo.

Kuti timvetse bwino zotsatira za kukhudzana ndi mitsempha ndi AMPH m'ma prairie voles achikazi, tinafufuza zotsatira za chithandizo chobwerezabwereza cha AMPH pa DA receptor mRNA expression ndi kumangirira m'madera osiyanasiyana a ubongo. Tinagwiritsa ntchito mlingo wa AMPH ndi njira yojambulira yomwe yawonetsedwa posachedwapa kuti imasintha DA receptor expression ndikusokoneza khalidwe la anthu m'ma prairie voles achimuna ( Liu et al., 2010 ). Deta yathu ikuwonetsa kuti mobwerezabwereza AMPH expression inakweza kwambiri kuchuluka kwa D1 receptor mRNA mu NAcc. Zotsatira zofanana, koma zosafunikira ( p < 0.07), zinawonedwa mu CP, zomwe zikusonyeza kuti AMPH ikhoza kukhala ndi zotsatira pa D1R mRNA expression m'derali. Ngakhale kusintha kumeneku mu gene expression, AMPH expression sinasinthe kuchuluka kwa D1-like receptor binding mu NAcc kapena CP. Pali mitundu iwiri ya D1-like receptors - D1 receptors ndi D5 receptors - zonse zomwe zinali ndi kuthekera kolembedwa ndi D1-like ligand yomwe idagwiritsidwa ntchito mu kuyesa kwathu kolumikizana ndi receptor. Komabe, popeza ma D5 receptor sapezeka mu NAcc ndi CP ( Missale et al., 1998 ; Tiberi et al., 1991 ), deta yathu ikusonyeza kusowa kwa kusintha, makamaka, mu kuchuluka kwa mapuloteni a D1 receptor. Mofananamo, malipoti am'mbuyomu m'mitundu ina ya makoswe asonyeza kuti kuwonetsedwa mobwerezabwereza ku AMPH kapena ma psychostimulants ena sikusintha modalirika kuyanjana kapena kuchuluka kwa ma D1 receptor m'madera awa a ubongo (kuti muwonenso onani ( Pierce ndi Kalivas, 1997 ; White ndi Kalivas, 1998 )), ngakhale kuti ma neuron a NAcc akuwonjezera kuyankha kwa ma D1 receptor agonists kwa mwezi umodzi pambuyo pa chithandizo cha mankhwala ( Henry et al., 1989 ; Henry ndi White, 1991 , 1995 ). Sitikunenanso kuti palibe kusintha kwa D2 receptor mRNA kapena D2-like receptor binding levels mu NAcc kapena CP mu female prairie voles pambuyo pa chithandizo cha AMPH, zomwe zikugwirizana ndi zomwe zimachitika m'makoswe ndi mbewa ( Richtand et al., 1997 ; Sora et al., 1992 ) ndi lingaliro lakuti NAcc D1 receptors imagwira ntchito yayikulu pakuyankha mobwerezabwereza kwa AMPH ( Berke ndi Hyman, 2000 ).

Chochititsa chidwi cha phunziroli ndi chakuti katemera wambiri wa AMPH wachepa kwambiri m'magulu a D2 receptor gene expression ndi D2-receptor kumangiriza mu VTA ya prairie voles. Mipata ya D2 mu VTA ili pamapiri amtendere a A10 DA neurons (DA akudziwitsidwa ndi neuroni zomwe zimachokera ku VTA ndipo zimayambira kumadera a mesocorticolimbic) (Aghajanian ndi Bunney, 1977; Mercuri et al., 1997; Oades ndi Halliday, 1987; White ndi Wang, 1984b). Zipangizozi zimagwira ntchito monga autoreceptors ndipo kutsegula kwawo kumabweretsa hyperpolarization ya membrane ya selo ndi kutetezedwa kwa kuwombera maselo (Mercuri et al., 1997) (kwa kafukufuku onani (Mercuri et al., 1992)), kuchepetsa kuchuluka kwa DA kutulutsidwa kumalo omwe akuwoneka ngati NAcc (Usiello et al., 2000). Momwemonso, D2 receptor blockade kapena kuchotsedwa kwa majeremusi chifukwa cha kusowa kwa maselo a A10 ndi kuwonjezereka kwa DA ku NAcc chifukwa cha zovuta zosiyanasiyana (Mercuri et al., 1997; Rouge-Pont et al., 2002). Choncho, kuchepetsedwa kwa ma DPNUMX receptors mu VTA omwe akupezeka mu phunziro lino kungasonyeze kuti AMPH-induced-regulation-regulator of somatodendritic autoreceptors mu prairie vole. Monga momwe magetsi amathandizira mofanana ndi kuchuluka kwa ntchito za A2 DA neurons (White ndi Wang, 1984a), zotsatirazi zingayambitse kumasulidwa kwa DA ndi kutsegula kwadzidzidzi ku NAcc. Mofananamo, kafukufuku wam'mbuyomu wagwira ntchito yowonjezera ya autotceptors yamtundu wa A10 DA neurons pambuyo pochitika mobwerezabwereza maganizo a psychostimulant, zomwe zimapangitsa kuchulukitsana kowonjezereka ndi kuyeza kwapadera kwa maselo a A10 DA (Henry et al., 1989) zomwe zingapitirire kwa masiku akutsatira mapeto a mankhwala osokoneza bongo (Ackerman ndi White, 1990). Ndikofunika kuzindikira kuti, ngakhale kuti D2 ndi D3 receptors amafotokozedwa mu VTA ndi locynastically presynaptically pa dopaminergic neurons (Diaz et al., 1995; Mercuri et al., 1997), posonyeza kuti kuchepa kwa D2-like receptor kumanga kungakhale chifukwa cha kusintha kwa onse kapena receptor subtypes. Kudziwa zenizeni zapadera zomwe zimakhudzidwa ndi kutuluka kwa AMPH ndizofunikira kuti tidziwitse deta, monga D2, koma osati D3, receptors, ndizofunika kuti autoreceptor iwononge DA neurons (Mercuri et al., 1997; Rouge-Pont et al., 2002). Komabe, momwe mawu a D3 amalandirira ndi otsika kwambiri mu VTA poyerekeza ndi a D2 receptors (Bouthenet et al., 1991), ndipo spiperone imasonyeza mgwirizano wapamwamba wa D2 kuposa wolandira D3 (Missale et al., 1998), zikutheka kuti zotsatira zomwe zikuchitika pa D2-ngati receptor kumangirira zikuyimira kuchepa m'magulu a D2, osati D3 receptors.

Ngakhale zotsatira za mitsempha ya m'mitsempha zomwe zimachitika mobwerezabwereza mwa akazi zikuwonetsa kufanana ndi zomwe zidapezeka kale m'ma vole a amuna ( Liu et al., 2010 ), kusiyana kwakukulu kuwiri kukuwonekera. Choyamba, ngakhale kuti AMPH idakulitsa mRNA ya receptor ya D1 mu NAcc mwa amuna ndi akazi onse, zotsatira za kuwonjezeka kwa kulembedwa kumeneku zidasungidwa mwa amuna okha (mwachitsanzo, akazi sanawonetse kusintha kulikonse mu kuchuluka kwa D1-like receptor binding pomwe AMPH idakulitsa kuchuluka kwa mapuloteni a receptor ya NAcc D1 mwa amuna). Kusiyana kumeneku kungakhale chifukwa cha kugwiritsa ntchito njira zosiyanasiyana zowerengera kuti azindikire zotsatira izi (mwachitsanzo, receptor binding idagwiritsidwa ntchito mwa akazi pomwe Western blotting idagwiritsidwa ntchito mwa amuna) kapena kungasonyeze zotsatira za kugonana kwa AMPH mobwerezabwereza pa ma receptors a D1 mkati mwa NAcc ya ma vole a prairie. Kachiwiri, chithandizo cha AMPH sichinakhudze momwe D2 receptor mRNA imaonekera mu VTA m'ma voles a amuna ( Liu et al., 2010 ), koma chinachepetsa kwambiri, komanso kuchuluka kwa D2 receptor, mwa akazi—zikusonyezanso kuti zotsatira za AMPH m'mitsempha ndi za amuna. Lingaliroli likuthandizidwa ndi zomwe zapezeka m'mitundu ina zomwe zimasonyeza kusiyana kwa kugonana m'ma gene pambuyo pa chithandizo cha AMPH ( Castner ndi Becker, 1996 ).

Kusintha kwa AMPH komwe kumachitika mu dongosolo la mesocorticolimbic DA kungakhale ndi zotsatirapo zofunika pa khalidwe la anthu m'madera otchedwa prairie voles. Monga tanenera kale, ma prairie voles akuluakulu aamuna ndi aakazi amapanga maubwenzi okhalitsa atatha kukwatirana ( Carter et al., 1995 ; Williams et al., 1992 ; Winslow et al., 1993 ) ndipo NAcc DA imawongolera khalidweli mwa amuna ndi akazi onse mwanjira yodziwika ndi receptor: D2-like receptor activation imathandizira ndipo D1-like receptor activation imaletsa mapangidwe a zokonda za okondedwa ( Aragona et al., 2003 , 2006 ; Aragona ndi Wang, 2009 ; Gingrich et al., 2000 ; Liu ndi Wang, 2003 ; Wang et al., 1999 ). Motero, kusintha komwe kumachitika ndi AMPH m'madera a ubongo a mesocorticolimbic, kuphatikizapo omwe afotokozedwa pano, kungakhale ndi zotsatirapo zazikulu pa khalidwe la maubwenzi awiri m'madera otchedwa prairie vole. Mwachitsanzo, mwa amuna, kuwonjezeka kwa AMPH kwa ma receptors ofanana ndi D1 mu NAcc kumaganiziridwa kuti ndiko komwe kumayambitsa kusokonekera kwa mapangidwe a zokonda za okondedwa ( Liu et al., 2010 ), chifukwa kuyambika kwa NAcc D1 receptor kumaletsa zokonda za okondedwa zomwe zimayambitsa kukwatirana ( Aragona et al., 2006 ). Kuphatikiza apo, kutsekedwa kwa mankhwala kwa ma receptors a D1 panthawi ya chithandizo cha AMPH modalira mlingo kunachotsa kusokonekera kwa mapangidwe a zokonda za okondedwa komwe kumayambitsa AMPH, zomwe zikusonyezanso kuti AMPH ikhoza kusokoneza mgwirizano wa awiriawiri kudzera mu njira yolumikizirana ndi D1 receptor ( Liu et al., 2010 ). Mwa akazi m'malo mwake, chifukwa cha kusowa kwa kuletsa kwa autoreceptor komwe kumatanthauzidwa ndi zomwe zapezeka pano (mwachitsanzo, kuchepa kwa D2 receptor expression mu VTA), kutulutsidwa kwa DA komwe kumayambitsa kukwatirana mu NAcc mwina kungakulitsidwe m'ma voles omwe amachiritsidwa ndi AMPH. Pamene kukwera kwakukulu kwa kuchuluka kwa DA kumayambitsa ma receptors otsika a D1 ( Richfield et al., 1989 ), neuroadaptation iyi ikhoza kukhala ndi zotsatira zofunika pa khalidwe pa mgwirizano wa anthu mwa akazi.

Pomalizira, kafukufuku wamakono akuwonetsa kuti mlingo woyenera wa khalidwe la AMPH umasintha maganizo a DA ndi mauthenga a receptor mkati mwa mesocorticolimbic DA dongosolo la azimayi aang'ono, omwe ndi ofunika kwambiri m'zochitika zamtundu wina wamtunduwu. Zotsatira izi zimapanga maziko a maphunziro a mtsogolo mwa azimayi a prairie voles kuti aone zotsatira za AMPH pa kugwirizanitsa awiri ndi njira zokhudzana ndi matenda.

4. Njira zowonetsera

4.1. Nyama

Akazi a mtundu wa prairie voles ( Microtus ochrogaster ) ochokera kumadera akum'mwera kwa Illinois anasiya kuyamwa ali ndi masiku 21 kenako anaikidwa m'mabedi apulasitiki (29×18×13 cm) okhala ndi zofunda za cedar chip. Anasungidwa pa 14:10 light-dark cycle (magetsi amayatsidwa nthawi ya 07:00 h) ndi mwayi wopeza chakudya ndi madzi. Kutentha kunasungidwa pa 21±1 °C. Nyama zonse zomwe zinagwiritsidwa ntchito mu kafukufukuyu zinali ndi zaka pakati pa 90 ndi 120. Kuyesera kunachitika motsatira malangizo a Institutional Animal Care and Use Committee ku Florida State University.

4.2. Malo ovomerezeka a malodi paradigm

Chipangizo cha CPP chinali chofanana ndi chomwe chafotokozedwa kale ndipo chinali ndi zikwama ziwiri zapulasitiki zomwe zinali zosiyana ndi maso (zoyera poyerekeza ndi zakuda) ndipo zinalumikizidwa ndi chubu chopanda kanthu ( Aragona et al., 2007 ; Liu et al., 2010 ). Tinagwiritsa ntchito njira yowongolera yomwe idapangidwa posachedwapa m'ma voles a amuna ( Liu et al., 2010 ). Mwachidule, ophunzira onse adapatsidwa mayeso asanafike mphindi 30 pa tsiku loyamba ndipo nthawi yomwe adagwiritsidwa ntchito mu chikwama chilichonse idawerengedwa. Chikwama chomwe munthu adakhala nthawi yochepa panthawi yoyeserera chisanatchulidwe chidatchulidwa ngati chikwama cholumikizidwa ndi mankhwala ndipo china chidatchulidwa ngati chikwama cholumikizidwa ndi saline. Kuwongolera kunachitika panthawi yamaphunziro awiri a mphindi 40 tsiku lililonse kwa masiku atatu otsatira (masiku 2-4). Pa nthawi ya maphunziro a m'mawa (0900 h), anthu adalandira jakisoni wa intraperitoneal (ip) wa 0.0, 0.1, 0.2, kapena 1.0 mg/kg d-AMPH sulfate (Sigma, St. Louis, MO, USA) wosungunuka mu saline, nthawi yomweyo asanaikidwe mu khola lolumikizidwa ndi mankhwala. Pa nthawi ya maphunziro a masana (1500 h), anthu adalandira jakisoni wa ip wa saline nthawi yomweyo asanaikidwe mu khola lolumikizidwa ndi saline. Ndondomeko yophunzitsira yoyeserera kawiri patsiku yagwiritsidwa ntchito mwa makoswe ( Campbell ndi Spear, 1999 ; Zhou et al., 2010 ) ndipo idagwiritsidwa ntchito mu kafukufuku wathu wakale m'ma voles aamuna a prairie ( Liu et al., 2010 ). Kuphatikiza apo, njira iyi idasankhidwa chifukwa deta yathu yoyesera sinasonyeze kusiyana kwa machitidwe pakati pa anthu omwe adalandira njira zoyesera zotsutsana ndi zokhazikika (deta yosasindikizidwa) komanso chifukwa njira zoyesera zoyesera ndi zosonkhanitsira minofu zinali zofunika kwambiri poyesa kuwonetsa kwa chizindikiro cha DA muzoyesa zotsatira komanso kufananiza mwachindunji ndi deta kuchokera ku ma voles achimuna aku prairie ( Liu et al., 2010 ). Pa tsiku lachisanu, anthu onse adayesedwa kuti awone ngati ali ndi CPP mu mphindi 30 pambuyo pa mayeso. Chiwerengero cha nthawi zomwe nyama zidadutsa pakati pa zikhomo chinalembedwa panthawi yoyeserera isanayambe komanso itatha ndipo idagwiritsidwa ntchito ngati chizindikiro cha ntchito ya locomotor.

4.3. Kukonzekera minofu

Anthu omwe adagwidwa adadulidwa mitu mwachangu mphindi 30 atalandira jakisoni mu Kuyesera 2 ndi maola 24 atalandira jakisoni womaliza mu Kuyesera 3 ndi 4. Ubongo wawo unachotsedwa mwachangu ndipo nthawi yomweyo unazizira pa ayezi wouma, usanasungidwe pa −80 °C. Ubongo wochokera ku Kuyesera 2 unagawika m'magawo pa 300 μm ndipo magawowo adasungunuka pa Superfrost/plus slides. Atlas ya ubongo wa makoswe a Paxinos ndi Watson ( Paxinos ndi Watson, 1998 ) idagwiritsidwa ntchito kuzindikira madera osiyanasiyana a ubongo, kuphatikiza PFC (Plates 8-10), NAcc (Plates 9-11), CP (Plates 10-12) ndi VTA (Plates 40-43), komwe ma punch a minofu ya m'mimba mwake wa 1 mm adatengedwa ( Chithunzi 2A ) ndikusungidwa pa −80 °C mpaka atakonzedwa. Ngakhale kuti si dera la ubongo la mesocorticolimbic, CP idaphatikizidwa mu kusanthula kwathu chifukwa, monga NAcc ndi PFC, imalandira thandizo la DAergic kuchokera ku VTA ( Oades ndi Halliday, 1987 ) koma sizikuwoneka kuti zikugwira ntchito mu DAergic regulation ya prairie vole partner preference formation ( Aragona et al., 2003 , 2006 ; Liu ndi Wang, 2003 ). Pa Mayeso 3 ndi 4, ubongo unadulidwa m'magawo 10 a magawo 14 μm omwe adayikidwa pa Superfrost/plus slides.

4.4. Kuchotsa DA ndi HPLC-ECD kufufuza

Kuchotsa DA kunachitika monga momwe tafotokozera kale ( Aragona et al., 2002 ), kupatula kuti zitsanzo za minofu zinajambulidwa mu 50 μL ya 0.1 M perchloric acid ndi 0.02% EDTA. Kuchuluka kwa DA kunayesedwa pogwiritsa ntchito high performance liquid chromatography yokhala ndi electrochemical detection (HPLC-ECD) monga momwe tafotokozera kale ( Curtis et al., 2003 ) ndi zosiyana izi. Gawo loyenda linali ndi 75 mM sodium dihydrogen phosphate monohydrate, 1.7 mM 1-octanesulfonic acid sodium salt, 0.01% triethylamine, 25 um EDTA, ndi 7% acetonitrile ndipo pH inasinthidwa kukhala 3.0 ndi 85% phosphoric acid. Kuthamanga kwa madzi kunali 0.5 ml/min. Malo ozungulira ndi malo otsetsereka anawerengedwa monga momwe tafotokozera kale ( Aragona et al., 2003 ). Malire ozindikira anali ~10 pg pa chitsanzo chilichonse.

4.5. Mu hybridisation for D1 ndi D2 receptor mRNA

Magulu ena a magawo a ubongo ochokera ku Experiment 3 adakonzedwa kuti alembedwe mu in situ hybridization labeling ya DA receptor mRNA. Antisense ndi sense riboprobes (zoperekedwa mowolowa manja ndi Dr. O. Civelli ku University of California, Irvine, CA), adagwiritsidwa ntchito polemba D1 ndi D2 receptor mRNA ndipo adakonzedwa monga momwe tafotokozera kale ( Liu et al., 2010 ). Ma probes adalembedwa payekhapayekha pa 37 ° C kwa ola limodzi mu transcription-optimized buffer yokhala ndi 0.5 μg/μl ya DNA template yoyenerera, [ 35 S]-CTP, 4 mM ya ATP, UTP, ndi GTP, 0.2 M dithiothreitol (DTT), RNasin (40 U/μl), ndi RNA polymerase (20 U/μl). Kenako template ya DNA idagayidwa ndi 1 U/μl DNaseI. Ma probes anatsukidwa pogwiritsa ntchito Chromatography Columns (Bio-Rad, Hercules, CA) kenako anasungunuka mu hybridization buffer yokhala ndi 50% deionized formamide, 10% dextran sulfate, 3× SSC, 10 mM sodium phosphate buffer (PB, pH 7.4), 1× Denhardt's solution, 0.2 mg/ml yeast tRNA, ndi 10 mM DTT kuti apeze 5×10 6 cpm/ml.

Chigawo cha ubongo chinayikidwa mu 4% paraformaldehyde mu mchere wa 0.1 M wa phosphate (PBS) pa 4 ° C kwa 20 min, odzozedwa mu PBS kwa 10 min, ndipo amachitidwa ndi 0.25% anticidhyde acheni mu triethanolamine (pH 8.0) ya 15 min kuchepetsa osamangika. Misisitolini inatsukidwa m'kati mwa 2 × saline sodium citrate (SSC), yotayika mwa kuwonjezeka kwa ethanol (ETOH) (70, 95, ndi 100%), ndi zouma.

Chingwe chilichonse chinalandira yankho la 100 μl hybridization lomwe linali ndi probe yoyenera ya 35 S-labeled, linatsitsidwa ndi chivundikiro kenako linayikidwa mu chipinda chonyowa pa 55 °C usiku wonse. Pambuyo pa kulowetsedwa, zophimbazo zinachotsedwa mu 2 × SSC, zophimbazo zinatsukidwa kawiri mu 2 × SSC kwa mphindi 5 kenako zinatsukidwa pa 37 °C kwa ola limodzi mu RNase buffer (8 mM Tris–HCl, 0.8 mM EDTA, ndi 0.4 M NaCl, pH 8.0) yokhala ndi 25 mg/ml RNaseA. Kenako, zophimbazo zinatsukidwa ndi kuchuluka kochepa kwa SSC (2 × SSC, 1 × SSC, ndi 0.5 × SSC) kwa mphindi 5 iliyonse ndipo zinayikidwa mu 0.1 × SSC pa 65 °C kwa mphindi 60. Pomaliza, zophimbazo zinabweretsedwa kutentha kwa chipinda, kuuma chifukwa cha kuchuluka kwa ETOH, ndikuumitsidwa ndi mpweya. Zigawo zinaikidwa pa filimu ya BioMax MR (Kodak, Rochester, NY) kwa nthawi zosiyanasiyana, kutengera ndi probe ndi dera lomwe likufuna, kuti apange ma autoradiogram abwino kwambiri. Pa NAcc ndi CP, zigawo zolembedwa za D1R ndi D2R mRNA zinaikidwa kuti zijambulidwe kwa maola 14 ndi 60, motsatana, pomwe zigawo zolembedwa za D1-like ndi D2-like receptor binding zinaikidwa kwa maola 15 ndi 6.5, motsatana. Pa VTA, zigawo zolembedwa za D2R mRNA zinaikidwa kwa maola 60 ndipo zomwe zolembedwa za D2-like binding zinaikidwa kwa maola 40. Kulamulira kwa sense RNA kunayesedwanso pa probe iliyonse ndipo sikunapereke chizindikiro, monga momwe zimayembekezeredwa.

4.6. Kujambula zithunzi za DA

Pa Kuyesera 4, magulu ena a magawo a ubongo adakonzedwa kuti awonetsetse kuti pali D1-like ndi D2-like receptor autoradiography. Ligand ya D1-like [ 125 I] SCH23982 ndi D2-like ligand [ 125 I] 2′-iodospiperone zidapezeka kuchokera ku PerkinElmer (Waltham, MA). DA receptor autoradiography idachitika monga momwe tafotokozera kale ( Aragona et al., 2006 ).

4.7. Kusanthula deta

Pa Kuyesera 1, CPP idafotokozedwa ndi kuwonjezeka kwakukulu kwa nthawi yomwe idagwiritsidwa ntchito mu khola lolumikizidwa ndi mankhwala panthawi yoyeserera pambuyo poyerekeza ndi mayeso asanachitike, monga momwe adayesedwera ndi mayeso a t- paired . Ntchito ya locomotor idawunikidwa pogwiritsa ntchito miyeso iwiri yobwerezabwereza ya ANOVA poyerekeza kuyenda kwa pre-vs. pambuyo poyesa (mkati mwa munthu) ndi kuyenda mwa chithandizo (pakati pa munthu). Pa Kuyesera 2, kuchuluka kwa DA kwa chitsanzo chilichonse kudasinthidwa pogwiritsa ntchito kuchuluka kwa mapuloteni onse a chitsanzocho kuti ayang'anire kuchuluka kwa minofu yomwe yasonkhanitsidwa. Kuchuluka kwa DA (pg/μg minofu) kenako kunasinthidwa kukhala peresenti ya kuchuluka kwa DA kwapakati pa saline control. Pa gawo lililonse la ubongo, kuchuluka kwa DA pakati pa magulu kudayerekezeredwa ndi mayeso a t- . Mu Zoyesera 3 ndi 4, ma autoradiogram adawunikidwa kuti awone kuchuluka kwa kuwala kwa mRNA kapena receptor binding mu NAcc, CP ndi VTA pogwiritsa ntchito pulogalamu ya zithunzi ya pakompyuta (NIH IMAGE 1.60) (PFC sinaphatikizidwe mu kusanthula chifukwa dera lino silinayankhe chithandizo cha AMPH mu Kuyesera 2). Kuchuluka kwa kusanthula kwa zithunzi za rostral/caudal kwa NAcc, CP ndi VTA kunali kofanana ndi komwe kunafotokozedwa mu Kuyesera 2. Kusiyana kwa neuroanatomical pakati pa NAcc ndi CP kunapangidwa pogwiritsa ntchito Paxinos ndi Watson rat brain atlas ( Paxinos ndi Watson, 1998 ) ngati chitsogozo, kutanthauza mawonekedwe a chizindikirocho ndi malo a anterior commissure. Zigawo za dera lililonse la ubongo zinagwirizanitsidwa mwachibadwa pakati pa anthu, ndipo njira za munthu aliyense payekha zinapezedwa poyesa kuchuluka kwa kuwala m'magawo atatu kuchokera kudera lililonse la ubongo pa nyama iliyonse. Kuchuluka kwa kumbuyo kunachotsedwa pa muyeso wa gawo lililonse. Kuchuluka kwa kuwala komaliza kunasinthidwa kukhala peresenti ya kuchuluka kwa saline control mean. Kusiyana kwa magulu mu mRNA kapena kuchuluka kwa ma link mkati mwa ubongo kunasanthulidwa pa DA receptor iliyonse pogwiritsa ntchito t -test. Mulingo wofunikira unayikidwa pa p <0.05.

Kuvomereza

Tikuthokoza Kevin Young ndi Adam Smith chifukwa chowerenga mozama malembawo. Ntchitoyi inathandizidwa ndi DAC31-25570 ku KAY, MHF31-79600 ku KLG, ndi DAR01-19627, DAK02-23048, ndi MHR01-58616 ku ZXW.

Mawu a M'munsi

Mafupikitsidwe: AMPH, amphetamine; ANOVA, kusanthula kusiyana; CP, caudate putamen; CPP, kukonda malo komwe kuli bwino; DTT, dithiothreitol; DA, dopamine; ETOH, ethanol; HPLC, high performance liquid chromatography; ip, intraperitoneal; PCF, medial prefrontal cortex; NAcc, nucleus accumbens; PBS, phosphate buffered saline; SSC, saline sodium citrate; PB, sodium phosphate buffer; VTA, ventral tegmental area

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