Amphetamine e fetola boitšoaro le mesocorticolimbic dopamine receptor polelo ho mosali a le mong oa likhutsana le mosali (2011)

Brain Res. Sengoloa se ngotsoeng; e fumaneha ho PMC Jul 25, 2011.

E hatisitsoe ka mokhoa o qetelle o hlophisitsoeng e le:

Brain Res. Jan 7, 2011; 1367: 213-222.

E phatlalalitsoe marang-rang Oct 8, 2010. Doi:  10.1016 / j.brainres.2010.09.109

PMCID: PMC3143067

NIHMSID: NIHMS312646

Moetso oa khatiso oa ho qetela oa mohatisi o fumaneha ho Resin ea Boko

Sheba lihlooho tse ling ho PMC hore Qotsa sehlooho se hatisitsoeng.

Eya ho:

inahaneloang

Re sa tsoa theha sechaba se rorisang monogamous prairie vole (Microtus ochrogaster) e le mohlala oa phoofolo eo ho eona ho hlahlojoang ho kenya letsoho ha mesocorticolimbic dopamine (DA) ho amphetamine (AMPH) - ho qobelle ho senyeha hoa boitšoaro ba sechaba. Ha boholo ba mosebetsi oa rona, ho fihlela joale, bo shebile haholo ho banna, 'me ho se tšoane ka liphapang tsa botona le botšehali ho tlalehiloe khafetsa lithutong tsa boitšoaro le tsa neurobiological ho AMPH, thuto ea hona joale e etselitsoe ho hlahloba litlamorao tsa boits'oaro le tsa neurobiological tsa kalafo ea AMPH libakeng tsa basali tsa prairie. Re sebelisitse paradigm ea sebaka se ikemetseng (CPP) ho tseba karoloana ea karabelo bakeng sa litlamorao tsa boitšoaro ba AMPH libakeng tsa basali tsa prairie, mme ra fumana boemo bo nang le maemo a tlase ho isa bohareng (0.2 le 1.0 mg / kg), empa eseng tlase haholo ( 0.1 mg / kg), litekanyetso tsa AMPH li qobelletse CPP. Hape re fumane hore ho pepesetsoa lethal e loketseng boits'oaro ba AMPH (1.0 mg / kg) ho bakile keketseho ea khatello ea DA maemong a nucleus accumbens (NAcc) le caudate putamen empa eseng ea medial prefrontal cortex kapa sebaka sa ventral tegmental (VTA). Qetellong, ho pepesetsoa khafetsa AMPH (1.0 mg / kg hang ka letsatsi bakeng sa matsatsi a 3 a latellanang; paradigm ea sindano e sa tsoa bontšoa ho fetola polelo ea receptor ea DA le ho senyeha ha tlamahano ea setsoalle le baeti ba banna ba rorisang) ho eketsehile D1, empa eseng D2, receptor mRNA ho le NAcc, le ho fokotsa D2 receptor mRNA le D2-receptor e tlamang ho VTA. Mmoho, lintlha tsena li bonts'a hore li-neuropransication tsa AMPH li fetola mesocorticolimbic DA ka tikoloho- le tsela e ikhethileng eo, ka nako eo, e ka bang le litlamorao tse tebileng boits'oarong ba sechaba maemong a basali ba rorisang basali.

Keywords: Psychostimulant, Nuklea e bokellanang, sebaka se ikhethileng sa Ventral, Autoreceptor, Pailing bonding

1. Selelekela

Lithethefatsi tsa tlhekefetso li nahanoa hore li fana ka taolo ea tsona e matla holim'a boitšoaro, ka karolo e 'ngoe, ka litlamorao tsa bona tsamaisong ea mesocorticolimbic dopamine (DA) (Kelley le Berridge, 2002; Nesse le Berridge, 1997; Nestler, 2004, 2005; Panksepp et al., 2002), potoloho ea neural e nang le lisele tse hlahisang DA tse hlahang sebakeng sa "ventral tegmental tegmental" (VTA) le projeke ho libaka tse fapaneng tsa bokapele, ho kenyeletsoa medial preambilial cortex (PFC) le nucleus accumbens (NAcc). Potoloho ena e bolokehileng haholo ea neural, e phethang karolo ea bohlokoa molatong oa boits'oaro bo tataisoang ke sepheo (Zahm, 2000) - Ho kenyelletsa boits'oaro bo khahlisang liphoofolo tsohle (mohlala, ho fepa (Narayanan et al., 2010; Palmiter, 2007)) le tseo e leng mefuta e ikhethileng (mohlala, ho tlamahana ka mefuta ea liphoofolo tse nyalanang.Aragona le Wang, 2009; Curtis et al., 2006; Young le al., 2010)) - e fetoloa haholo ke ho pepesehela lithethefatsi tsa tlhekefetso. Mohlala, ho pepeseha ka matla le / kapa khafetsa lithethefatsi tsa psychostimulant tsa tlhekefetso, joalo ka cocaine kapa amphetamine (AMPH), ho fella ka tokollo e fetotsoeng ea DA, polelo ea DA receptor le kutlo, le neuronal morphology kahare ho libaka tsa boko ba mesocorticolimbic (Henry et al., 1989; Henry le White, 1995; Hu et al., 2002; Nestler, 2005; Pierce le Kalivas, 1997; Robinson et al., 2001, 1988; Robinson le Kolb, 1997; Bosoeu le Kalivas, 1998). Ho nahanoa hore li-neuroadaptations tsena li ka ba le liphetoho tse tlisoang ke lithethefatsi ho litloaelo tsa liphoofolo (Robinson le Becker, 1986), ho kenyelletsa boitšoaro ba sechaba (bakeng sa tlhahlobo, bona (Young le al., 2011)).

Mosebetsi oa morao-rao o tsoang laboratoring ea rona o thehile viri ea prairie e le mohlala oa liphoofolo ho etsa lipatlisiso mabapi le ho kenya letsoho ha mesocorticolimbic DA litlamorao tsa lithethefatsi tsa tlhekefetso ho litloaelo tsa sechaba (Liu et al., 2010). Li-voiri tsa Prairie ke litoeba tse tsoang sechabeng tse etsang khetho ea molekane ea tloaelaneng (ke hore, khetho ea molekane) kamora ho lula hammoho le / kapa ho nyalana (Insel et al., 1995; Williams et al., 1992; Winslow et al., 1993), le mesocorticolimbic DA - haholo-holo neurotransication ea DA ho NAcc - e bohlokoa ts'ebetsong ena (Aragona et al., 2003, 2006; Aragona le Wang, 2009; Curtis et al., 2006; Gingrich et al., 2000; Liu le Wang, 2003; Wang et al., 1999; Young le al., 2010). Ho khahlisang, ho pepesetsoa ha AMPH ho fetola haholo tšebetso ea mesocorticolimbic DA le neurotransmission ho li-voes tsa banna tsa prairie. Mohlala, ente e le 'ngoe ea AMPH e eketsehile haholo maemo a DA a kantle ho Nacc (Curtis le Wang, 2007). Ho ekelletsa moo, matsatsi a mararo a tšibollo ea AMPH, e ileng ea etsa hore ho thehoe mofuta oa boikhethelo ba sebaka (CPP) ha e penta ka tikoloho, e fetotseng polelo ea DA receptor ho NAcc ka mokhoa o ikhethileng oa receptor (Liu et al., 2010). Haholo-holo kalafo ena e sebelisang lithethefatsi e ne e thibela ho thehwa ha litabatabelo tsa balekane.Liu et al., 2010).

Leha lithuto tse hlalositsoeng kaholimo li thehile sebaka sa tumello e le mohlala o motle haholo oa ho hlahloba tšitiso e tlatselitsoeng ea AMPH ea kamano ea batho le mekhoa ea bona e tlase ea motheo, ba ne ba etsoa feela ba batona. Ka lebaka leo, re tseba ho honyenyane ka litla-morao tsa boits'oaro le methapo ea bophelo ba AMPH libakeng tsa basali tsa praemia. Bopaki bo teng ho fana ka maikutlo a hore li-voes tsa prairie tsa basali li na le kutloelo-bohloko haholo ho li-AMPH ho feta li-voes tsa basali tsa praemia.Aragona et al., 2007) le lithuto tsa mefuta e meng hangata li tlaleha liphapang tsa thobalano litabeng tsa boitšoaro le tsa neurobiological tsa AMPH le lithethefatsi tse ling tsa psychostimulant tsa tlhekefetso (Becker le Hu, 2008; Fattore et al., 2008; Lynch, 2006). Mohlala, likhoto tsa basali li bonts'a ts'ebetso e kholo ea ts'ebetso le ho kenella ka mokhoa o potlakileng oa maikutlo a boitšoaro mabapi le AMPH (Camp le Robinson, 1988), fumana cocaine le methamphetamine ho itaola ka potlako (Hu et al., 2004; Lynch, 2006; Lynch le Carroll, 1999; Roth le Carroll, 2004), hape o bonts'a khothatso e kholo ea ho fumana li-psychostimulants (Roberts le al., 1989; Roth le Carroll, 2004) ho feta banna. Ho feta moo, phapang ea thobalano e hlokometsoe karabelong ea neurobiological ho li-psychostimulants, ho kenyelletsa le phapang ea tokollo ea DAPH e hlahisang AMPH (Becker, 1990; Becker le Ramirez, 1981), Metabolism ea DA (Camp le Robinson, 1988), le polelo ea pele ea mofuta oa pele (Castner le Becker, 1996). Ho etsa lipatlisiso tsa litlamorao tsa neurobiological tsa AMPH ka li-voes tsa basali tsa basali ho bohlokoa haholo ho theha mohlala oa tlholo ea lithuto tsa tlhahlobo ea likamano lipakeng tsa lithethefatsi tsa tlhekefetso, boits'oaro ba sechaba, le mesocorticolimbic DA.

Boithuto ba hajoale bo ne bo etselitsoe ho lekola litlamorao tsa boits'oaro le maikutlo a ho pepeseha hoa AMPH phuleng ea basali ba rorisang basali. Re sebelisitse paradigm ea CPP eo pele e neng e thehiloe ka li-voes tsa banna ba rorisang (Liu et al., 2010) ho hlahloba boits'oaro bo amanang le litekanyetso tse fapaneng tsa AMPH ho basali. Ha basali ba tloaetse ho bonts'a maikutlo a maholo a boitšoaro ho AMPH ho feta banna (Aragona et al., 2007; Becker et al., 2001; Camp le Robinson, 1988), re fane ka maikutlo a hore li-voes tsa basali tsa basali li tla theha CPP ka tekanyetso e tlase ea AMPH ho feta tse tlalehiloeng banna. Re boetse ra hlahloba litlamorao tsa ho pepesetsoa ha AMPH ho mahlaseli a DA le polelo ea lipono tsa DA le ho tlama libakeng tse fapaneng tsa boko ba mesocorticolimbic. Re ile ra nahana hore tlhahiso ea AMPH e tla fetola khatello ea DA le polelo ea DA ea receptor ka mokhoa o ikhethileng. Liphetho tse tsoang thutong ea morao-rao li tla fana ka leseli le sebetsang bakeng sa mosebetsi oa kamoso o hlahlobang litlamorao tsa AMPH ho boitšoaro ba sechaba ho basali ba mofuta ona.

2. Liphetho

2.1. Teko 1: Boemo ba AMPH bo kenyellelitse CPP

Teko 1 e thehile mofuta oa karabelo ea karabelo bakeng sa CPP e kenyellelitsoeng lipapaling tsa basali tsa basali. Bakeng sa ho bapisa tekanyetso ea karabelo le karabelo ea basali le banna, re sebelisitse paradigm e tšoanang hantle le e sa tsoa qaloa li-voes tsa banna prairie (Liu et al., 2010). Lingolo li ile tsa abeloa ka nepo ho e 'ngoe ea lihlopha tse' ne tsa liteko tse ileng tsa khetholloa ke khatello ea AMPH [0.0 (n= 20), 0.1 (n= 8), 0.2 (n= 12), kapa 1.0 mg / kg (n= 13)] ba amohetse nakong ea maemo a ntlafalitsoeng a AMPH (bona lits'ebetso tsa Tlhahlobo bakeng sa lintlha). Lithuto tsohle li ile tsa lekoa bakeng sa ho ba teng ha CPP naheng e se nang lithethefatsi ka letsatsi le latelang seboka sa ho qetela sa maemo. CPP e hlalositsoe ke keketseho e kholo ea nako e sebelisitsoeng khubung e kentsoeng lithethefatsi nakong ea tlhahlobo ea kamora ho bapisoa le tlhahlobo ea pele ho teko.

Lintho tse tšoaroang ka letsoai le le leng [0.0 mg / kg; t(19)= 1.65; p<0.12] kapa letsoai le nang le tlaase ka ho fetisisa [0.1 mg / kg; t(7)= 1.89; pKhakanyo ea AMPH ea <0.90] e sebelisitse lipalo tse lekanang ka nako ka phapusing e nang le lithethefatsi pele le kamora boemo mme ka hona ha ea ka ea theha CPP (Setšoantšo sa 1A). Sebakeng seo, lithuto tse tšoaroang ka 0.2 [t(11)= 2.77; p<0.02] kapa 1.0 mg / kg [t(12)= 2.53; p<0.03] AMPH e bontšitse CPP e matla, kaha ba qetile nako e ngata haholo ka phapusing e nang le lithethefatsi nakong ea tlhahlobo ea kamora 'mele ho feta ea pele ho teko (Setšoantšo sa 1A). Ha ho na phapang ea ts'ebetso ea locomotor e hlokometsoeng kahare kapa lipakeng tsa lihlopha pele ho kapa kalafo ea lithethefatsi (Setšoantšo sa 1B).

Feie. 1 

Amphetamine (AMPH) - e ntlafalitsoeng le maemo a boikhethelo ba sebaka (CPP) le ts'ebetso ea locomotor libakeng tsa basali tsa prairie. Basali ba fumaneng 0.0 (saline feela) kapa 0.1 mg / kg AMPH nakong ea matsatsi a 3 ea maemo ha baa ka ba theha CPP, kaha ba ile ba qeta nako e lekanang ...

2.2. Teko ea 2: Phekolo ea AMPH e fetotsoe mesocorticolimbic DA mahloriso

Teko 2 e ile ea hlahloba phello ea kalafo e le 'ngoe ea AMPH ho mahloriso a DA libakeng tse khethiloeng tsa boko ho kenyeletsoa PFC, NAcc, caudate putamen (CP) le VTA (Setšoantšo sa 2A). Lihlooho li ile tsa abeloa ka mokhoa o sa reroang ho e 'ngoe ea lihlopha tse peli tsa liteko tse amohetseng ente ea IP e le ngoe ea 0.9% saline (n= 6) kapa 1.0 mg / kg AMPH e qhibilihile ka letsoai (n= 6). Tekanyetso ena e ile ea khethoa hobane e ne e lekane ho susumetsa CPP ho basali (boits'oaro ba 1) le li-voes praee voles (Aragona et al., 2007; Liu et al., 2010), e bonts'a ts'ebetso ea eona ea boitšoaro ho batona le ba batšehali. Lithuto tsohle li ile tsa etsoa sehlabelo ka 30 min kamora ho kenngoa ente, mme khatello ea DA ka liseleng tsa bona tsa boko e ile ea lekanngoa ho sebelisoa ts'ebetso e phahameng ea chromatography e nang le tlhahlobo ea motlakase (HPLC-ECD).

Feie. 2 

Litlamorao tsa ente e le 'ngoe ea AMPH (1 mg / kg) ho mahloriso a DA libakeng tsa boko ba mesocorticolimbic. Papiso ea Schematic ea libaka tsa tishu-punch bakeng sa medial prefrontal cortex (PFC), li-nucleus accumbens (NAcc), caudate putamen (CP) le ventral ...

Phekolo e le 'ngoe ea AMPH e fetotse khatello ea DA ka mokhoa o ikhethileng kahare ho sistimi ea mesocorticolimbic DA (Setšoantšo sa 2B). Lintho tse tšoaroang ke AMPH li bile le khatello e phahameng haholo ea DA ho NAcc [t(10) = 2.06; p<0.03] le CP [t(10)= 2.07, p<0.03] ho feta taolo e entsoeng ka letsoai. Leha ho le joalo, ha ho liphapang tsa sehlopha tse fumanoeng ho PFC [t(10)= 0.03; p<0.49] kapa VTA [t(10)= 1.41; p<0.09].

2.3. Liteko 3 le 4: phetiso e pheta-phetoang ea AMPH e hlalosang mantsoe a receptor mRNA ebile e tlama

Liteko 3 le 4 li ile tsa hlahloba litlamorao tsa kalafo ea AMPH e phetoang ho D1 receptor le D2 receptor mRNA expression le D1-like le D2-like receptor. Liteko tsa pejana tsa li-voes tsa praemia tsa banna li bontšitse hore ho pepesetsoa hangata hoa AMPH (1.0 mg / kg hang ka letsatsi bakeng sa matsatsi a 3 a latellanang) ho fetola haholo polelo ea DA receptor ho NAcc 24 h kamora ho entelo ea hoqetela le hore phetoho ena e ka bakela phello ea ts'ebetso ea AMPH. tlamo ea botsoalle (Liu et al., 2010). Ka hona, re sebelisitse paradigm ena ea jwala ea lithethefatsi ho etsa lipatlisiso ka litlamorao tsa ho pepesoa hoa AMPH hangata ho basali. Lingoloa li ile tsa abeloa ka le leng sehlopheng se le seng sa lihlopha tse amohetseng liente tsa saline (taolo, n= 6) kapa letsoai le nang le 1.0 mg / kg AMPH (n= 8), hang ka letsatsi ka matsatsi a mararo a latellanang. Lithuto tsohle li ile tsa etsoa sehlabelo 24 h kamora ho ente ea ho qetela. Methapo ea D1 receptor mRNA le D1-receptor binding e ne e lekantsoe ho NAcc le CP ha D2 receptor mRNA le D2-like receptor binding li ne li lekantsoe ho NAcc, CP le VTA. D1R mRNA le li-receptor tse kang D1 tse tšoanang ha lia ka tsa lekanngoa ho VTA ka lebaka la ho haella ha boteng ba bona sebakeng sena sa boko (Weiner et al., 1991).

Ponaletso e phetoang khafetsa ea AMPH e fetole polelo ea DA receptor mRNA ka mokhoa o amohelang- hape le ka kotloloho sebakeng. Lintho tse amohetseng kalafo ea AMPH tse phetoang li bontšitse boemo bo holimo haholo ba ho ngoloa ha D1 receptor mRNA ho NAcc [t(12)= 2.85; p <0.01], empa eseng CP [t(12)= 1.96; p <0.07], ho feta litsamaiso tse entsoeng ka letsoai (Lifeiga. 3A le B). Ha ho na liphapang tsa sehlopha tse fumanoeng ho ngoloa ka D2 receptor mRNA ebang ke NAcc [t(12)= 1.56; p <0.14] kapa CP [t(12)= 1.79; p <0.10] (Likokonyana. 3C le D). Leha ho le joalo, kalafo e phetoa ea AMPH e fokotsehile haholo boemo ba D2 receptor mRNA ho VTA [t(12)= 3.11; p <0.01] (Likokonyana. 3Eand F).

Feie. 3 

Litlamorao tsa taolo e pheta-pheto ea AMPH (1 mg / kg / letsatsi bakeng sa matsatsi a 3 a latellanang) ho ho ngolla ka dopamine receptor mRNA sebakeng sa basali sa prairie vole. Phekolo e phetoang khafetsa ea AMPH e ile ea eketsa li-receptor tsa D1 (D1R) ka har'a li-nucleus accumbens (NAcc), empa eseng ...

Ho pepesetsoa AMPH khafetsa ho ne ho sena phello ho receptor e kang D1 (Lifeiga. 4A le B) kapa D2-receptorLikokonyana. 4C le Dmaemo a tlamang ho NAcc [D1-like: t(12)= 0.40; p <0.35, D2-joalo: t(12)= 0.77; p<0.23] kapa CP [D1-like: t(12)= 0.63; p<0.27, D2-joalo: t(12)= 0.91; p<0.19]. Leha ho le joalo, lihlooho tse tšoaroang ke AMPH li ne li na le boemo bo tlase haholo ba D2-like receptor e tlamang ho VTA ho feta taolo e kenngoeng ka letsoai [t(12)= 1.91; p<0.04] (Likokonyana. 4E le F).

Feie. 4 

Litlamorao tsa taolo e pheta-pheto ea AMPH (1 mg / kg / letsatsi bakeng sa matsatsi a 3 a latellanang) maemong a tlamang a dopamine sebakeng sa basali sa prairie vole. Phekolo e phetoang khafetsa ea AMPH ha ea ka ea fetola maemo a kang D1-like (A le B) kapa D2-like receptor binding (C le D) ka har'a ...

3. Puisano

Phuputso e teng hona joale e fuputse litlamorao tsa boits'oaro le boteng ba ho pepesetsoa hoa AMPH libakeng tsa basali tsa prairie. Ka kopanelo, lintlha tsa rona li bonts'a hore AMPH e na le litlamorao tse tsamaeang le tekanyetso boitshwarong, e eketsa tsitsipano ea DA ho NAcc le CP, 'me e fetola polelo ea mofuta oa receptor le ho ikamahanya ka mokhoa o ikhethileng. Lintlha tsena li ka qetella li fana ka leseli le sebetsang bakeng sa lithuto tsa nako e tlang tse etsang lipatlisiso tsa litlamorao tsa AMPH mabapi le boitšoaro ba sechaba ho basali ba mofuta ona.

CPP e bonts'a khetho ea moelelo oa tikoloho o pentiloeng ka matlafatso ea mantlha (Bardo le Bevins, 2000) - ntlheng ena, AMPH - 'me hangata e sebelisoa e le mokhoa o nepahetseng, o sa tobang, ka kotloloho ea moputso oa lithethefatsi. Liphetho tsa rona li bonts'a li-voes tsa basali tsa basali li theha CPP kamora kalafo e nang le tekanyetso e tlase le e bohareng ea AMPH. Ha re bapisoa le sephetho sa rona sa morao-rao sa li-voes tsa praemete tsa banna tse fumanoeng li sebelisa paradigm e tšoanang ea CPP (Liu et al., 2010), data tsena, hammoho, li bonts'a phetoho ea letsoho le letšehali tseleng ea karabelo-karabelo bakeng sa CPP libakeng tsa basali tsa prairie. Ka ho khetheha, 0.2 mg / kg kapa tekanyetso e phahameng ea AMPH e ile ea qobella CPP ho basali, athe 1.0 mg / kg kapa tekanyetso e phahameng ea AMPH e ne e hlokahala bakeng sa ho kenyelletsa CPP ho banna (Liu et al., 2010). Phetoho ena e tlohelang mokokotlong oa batho ba basali e tsamaisana le thuto e fetileng ho li-voes tsa prairie tse sebelisitseng paradigm e fapaneng.Aragona et al., 2007), hape e fana ka maikutlo a hore basali ba tsotella litlamorao tsa boits'oaro, 'me mohlomong ba kotsing ea ho fumana melemo, ea AMPH ho feta banna-e fumanoeng e bontšitsoe kamehla mefuta e meng (Camp le Robinson, 1988; Hu et al., 2004; Lynch, 2006; Lynch le Carroll, 1999; Roberts le al., 1989; Roth le Carroll, 2004) mme seo se ka ba le litlamorao tsa bohlokoa bakeng sa litlamorao tsa AMPH ho boitšoaro ba sechaba maemong a basali ba rorisang basali.

Phuputsong e teng hona joale, re fumane hape hore tsamaiso ea AMPH - ka tekanyetso e amanang le boits'oaro (1.0 mg / kg) bakeng sa li-voes tsa basali tsa basali - ho eketseha ha khatello ea DA ho NAcc le CP empa eseng PFC kapa VTA. Liphetho tsena li bonts'a ntlafatso e ikhethileng e amanang le AMPH ea tikoloho ea khatello ea DA. Joalo ka ha lithuto tsa pejana ho mefuta e mengata li bonts'itse ts'ebetso ea ho lokolloa ha kantle ho DA ho NAcc le CP nakoana kamora ho entetsoa ke AMPH (Cho et al., 1999; Ho qhekella le Bowyer, 1999; Curtis le Wang, 2007; Di Chiara et al., 1993; Drevets et al., 2001), khatello e eketsehang ea DA libakeng tsena lithutong tsa hona joale e ka ba ka lebaka la ntlafatso e entsoeng ke AMPH ea tokollo ea DA. Leha ho le joalo, kaha khatello ea DA e boetse e anngoe ke synthesis ea DA le metabolism, monahano ona o hloka ho lekoa litekong tse ling. Ntle le moo, ho bile le mokhoa o hlokomelehang oa phokotso ea khatello ea DA setulong sa VTA kamora ho pepesetsoa hoa AMPH libakeng tsa basali tsa prairie. Le ha phello ena e ne e se bohlokoa (p <0.09), ho hlokahala liteko tse ling ho laola phello ea AMPH holima mahloriso a DA sebakeng sena sa boko.

Ho utloisisa le ho feta litlamorao tsa ho pepeseha hoa AMPH libakeng tsa basali tsa basali, re ile ra etsa lipatlisiso ka litlamorao tsa kalafo ea AMPH khafetsa ho polelo ea DA receptor mRNA le ho tlama likarolong tse fapaneng tsa boko. Re sebelisitse lethal dose la AMPH le injara paradigm eo haufinyane e bonts'itsoeng ho fetola polelo ea DA receptor le ho nyenyefatsa boits'oaro ba sechaba maemong a banna ba prairie (Liu et al., 2010). Lintlha tsa rona li bontša hore ho pepesetsoa khafetsa AMPH ho eketsehile haholo boemo ba D1 receptor mRNA ho NAcc. E tšoanang, empa ha e bohlokoa (p <0.07), phello e ile ea tsejoa ho CP, e bonts'a hore AMPH e kanna ea ba le litlamorao ho polelo ea D1R mRNA le tikolohong ena. Leha ho na le liphetoho tse mabapi le liphatsa tsa lefutso, tlhahiso ea AMPH ha ea ka ea fetola boemo ba tlamo e amohelang D1-like receptor ho NAcc kapa CP. Hona le mefuta e 'meli ea li-receptor tse kang D1 - li-receptor tsa D1 le li-receptor tsa D5 - tseo ka bobeli li neng li na le monyetla oa ho ngoloa ke ligand ea D1 e sebelisitsoeng tekong ea rona ea ho tlamella receptor. Leha ho le joalo, kaha li-receptor tsa D5 ha li eo ho NAcc le CP (E tsamaisang hampe al al., 1998; Tiberi et al., 1991), data ea rona e fana ka tlhahiso ea ho hloka phetoho, haholo-holo, maemong a liprotheine tsa D1 tsa receptor. Ka mokhoa o ts'oanang, litlaleho tsa pejana ho mefuta e meng ea litoeba li bonts'itse hore ho pepesetsoa khafetsa ho AMPH kapa li-psychostimulants tse ling ha ho fetole ka mokhoa o tšepahalang ts'ebetso ea kamano ea D1 receptor kapa letsoalo libakeng tsena tsa boko (bakeng sa tlhahlobo ea bona (Pierce le Kalivas, 1997; Bosoeu le Kalivas, 1998)), leha e le ho ntlafatsa ho arabela ha li-neurons tsa Nacc ho li-agonists tsa D1 tsa receptor ho fihlela khoeli e le 'ngoe ka mor'a kalafo ea lithethefatsi (Henry et al., 1989; Henry le White, 1991, 1995). Hape ha re tlalehe hore ha ho na liphetoho lipapaling tsa receptor mRNA tsa D2 kapa D2 tse tšoanang le NAcc kapa CP libakeng tsa basali tsa kamora kalafo kamora kalafo ea AMPH.Richtand et al., 1997; Sora et al., 1992) le tlhahiso ea hore Nacc D1 receptors e bapala karolo e kholo ho arabiseng ho pepesoa hoa AMPH ka makhetlo a mangata (Berke le Hyman, 2000).

Phumano e khahlisang thutong ea hona joale ke hore kalafo e phetoang ea AMPH e fokotsitse haholo maemo a mofuta oa D2 receptor gene le D2-like receptor e tlamang ho VTA ea li-voes tsa basali tsa prairie. Li-receptor tsa D2 ho VTA li libakeng tsa somatodendritic tsa A10 DA neurons (li-neurons tsa projeke tsa DA tse hlahang VTA le projeke ea libaka tsa mesocorticolimbic) (Aghajanian le Bunney, 1977; Mercuri et al., 1997; Maobane le Halliday, 1987; Bosoeu le Wang, 1984b). Li-receptor tsena li sebetsa e le li-autoreceptors mme ts'ebetso ea tsona e lebisa ho hyperpolarization ea membrane ea sele le thibelo ea ho thunngoa ha sele (Mercuri et al., 1997) (bakeng sa tlhahlobo bona (Mercuri et al., 1992)), e fokotsa palo ea DA e lokollotsoeng libakeng tse amehang joalo ka NAcc (Usiello et al., 2000). Ka hona, D2 receptor blockade kapa gene Deletion e baka ho haella ha A10 cell inhibition le ho phatloha ho hoholo hoa DA ho NAcc ho arabela mefuta e fapaneng ea bo susumetsang (Mercuri et al., 1997; Rouge-Pont et al., 2002). Ka hona, ho fokotseha ha li-receptor tsa D2 ho VTA e boletsoeng thutong ea morao-rao ho ka supa taelo ea AMPH e thehiloeng tlaase ea somatodendritic autoreceptors sebakeng sa basali sa prairie vole. Joalo ka ha segokotso sa auto-receptor se amana ka kotloloho le sekhahla sa tšebetso ea li-neuron tsa A10 DA (Bosoeu le Wang, 1984a), phello ena e ka lebisa ho nts'etsopele ho lokolloe ha DA le phetisetso ea methapo ho NAcc. Ka mokhoa o ts'oanang, lipatlisiso tsa pejana li bonts'itse subsensitivity ea somatodendritic autoreceptors ho li-neuron tsa A10 DA kamora ho pepesetsoa khafetsa psychostimulant, ho fella ka ts'ebetso e eketsehang ea sekhahla le sekhahla sa ho thunya ha basal sa lisele tsa A10 DA (Henry et al., 1989) e ka lulang matsatsi a latelang ho fela ha kalafo ea lithethefatsi (Ackerman le White, 1990). Ho bohlokoa ho hlokomela, leha ho le joalo, hore li-receptor tsa D2 le D3 li hlahisoa ho VTA le li-localised presynaptically on dopaminergic neurons (Diaz et al., 1995; Mercuri et al., 1997), ho bonts'a hore phokotseho ea hajoale ea li-receptor tse kang D2 e kanna ea hlahisoa ke liphetoho tse teng kapa ka bobeli ba li-receptor subtypes. Tsebo ea "receptor subtype" e anngoeng ke tlhahiso ea AMPH e bohlokoa ho toloko ea rona ea data, joalo ka D2, empa eseng D3, li-receptors, li hlokahala bakeng sa thibelo ea autoreceptor ea li-neurons tsa DA (Mercuri et al., 1997; Rouge-Pont et al., 2002). Le ha ho le joalo, ha polelo ea li-receptor ea D3 e le tlase haholo ho VTA e amanang le D2 receptors (Bouthenet et al., 1991), 'me spiperone e bonts'a tumellano e phahameng ea D2 ho feta D3 receptor (E tsamaisang hampe al al., 1998), ho ka etsahala hore litlamorao tsa hona joale tsa D2-receptor e tlamang li emetse ho fokotseha hoa maemo a D2, ho fapana le li-receptors tsa D3.

Ha litla-morao tsa phetisetso ea AMPH khafetsa ho basali li bonts'a ho ts'oana le ho fumanoeng pejana ho li-voes praee voles (Liu et al., 2010), ho hlaha liphapang tse peli tsa bohlokoa. Taba ea pele, le ha boiphihlelo ba AMPH bo eketsehile D1 receptor mRNA ho NAcc ka bobeli ba bong, pheko e sebetsang ea ts'ebetso ea phetoho e ne e bolokiloe feela ho ba batona (ke hore, basali ha baa ka ba bontša liphetoho lipakeng tsa li-receptor tsa D1 tse kang li-receptor ha AMPH e ntse e eketsa maemo a proteni ea receptor ea D1 ho banna). Liphapang tsena li ka bakoa ke ts'ebeliso ea mekhoa e fapaneng ea ho lekana ho bona litlamorao tse sebetsang. ea voles of prairie. La bobeli, kalafo ea AMPH e ne e se na litlamorao ho polelo ea D1 receptor mRNA ho VTA ho li-voles tsa banna (Liu et al., 2010), empa ea e fokolitse haholo, hammoho le maemo a tlamang a D2, ho basali - a fana ka tlhahiso ea hore litlamorao tsa neurobiological tsa AMPH li bua ka thobalano. Mohopolo ona o ts'ehelitsoe ke lipatlisiso tsa mefuta e meng tse bonts'ang phapang ea thobalano ho polelo ea gene kamora kalafo ea AMPH (Castner le Becker, 1996).

Liphetoho tse kentsoeng ke AMPH tsamaisong ea mesocorticolimbic DA li ka ba le litlamorao tsa bohlokoa boits'oarong ba sechaba libakeng tsa prairie voles. Joalokaha ho boletsoe pejana, lihlopha tsa batho ba rorisang ba batona le ba batšehali ba theha maqhama a mabeli kamora ho nyalana (Carter et al., 1995; Williams et al., 1992; Winslow et al., 1993) mme NAcc DA e laola boitšoaro bona liketsong tsa botona le botšehali ka tsela e ikhethileng: D2-like receptor activation le D1-like activation receptor e thibela likhetho tsa molekane.Aragona et al., 2003, 2006; Aragona le Wang, 2009; Gingrich et al., 2000; Liu le Wang, 2003; Wang et al., 1999). Kahoo, liphetoho tse bakiloeng ke ts'ebetso ea AMPH libakeng tsa boko ba mesocorticolimbic, ho kenyeletsoa tse boletsoeng mona, li ka ba le litlamorao tse matla boits'oarong ba bonngoe sebakeng se rorisang. Ho banna, ho etsa mohlala, keketseho ea AMPH e kenyellelitsoeng ho li-receptors tse kang D1 ho NAcc ho nahanoa hore e baka tšenyo e mpe ea ts'ebetso ea molekane ea molekane oa (AMPH).Liu et al., 2010), joalo ka ha Nacc D1 receptor activation e thibela likhetho tsa molekane oa hau tsa mating.Aragona et al., 2006). Ho kenyelletsa moo, pharmacological blockade ea D1 receptors nakong ea phekolo ea AMPH-ka ts'ebetso e felisitse ts'ebetso ea AMPH-induction e bakoang ke khetho ea molekane, e ntse e tsoela pele ho supa hore AMPH e ka senya botsitso ka mochine oa li-receptor-mediated oa D1 (Liu et al., 2010). Ho basali ho fapana le hoo, ka lebaka la ho haella ha inhibition ea autoreceptor e boletsoeng ke liphetho tsa hajoale (ke hore, ho fokotsehile polelo ea D2 receptor ho VTA), ho lokolloa ha mathe ho tsoa ho DA ho NAcc ho kanna ha ntlafatsoa ho liemahale tse tšoaroang ke AMPH. Joalo ka bophahamo bo matla litlamong tsa DA bo kenya tšebetsong litsoalo tse tlase tsa D1 receptors (Richfield et al., 1989), neuroadaptation ena e kanna ea ba le litlamorao tsa bohlokoa tsa boitšoaro tlamahanong ea basali ho basali.

Qetellong, thuto ea morao-rao e bonts'a hore tekanyetso e sebetsang ea AMPH e fetola maikutlo a DA le ho amohela li-receptor kahare ho sistimi ea mesocorticolimbic DA ea li-voes tsa basali tsa basali, potoloho ea bohlokoa e kenyelletsang boits'oaro bo bobe ba sechaba ba mofuta ona. Liphetho tsena li fana ka motheo oa lithuto tsa nako e tlang lithutong tsa basali tsa basali ho hlahloba litlamorao tsa AMPH ho bonding le mekhoa e amanang le methapo ea kutlo.

4. Tsamaiso ea liteko

4.1. Liphoofolo

Li-voiri tsa basali tse isitsoeng botlamuoeng (Microtus ochrogaster) a tsoa bathong ba ka boroa ho Illinois a ile a khoesoa matsatsing a 21 a le lilemo li ntan'o ba a lula ka liaparong tsa bana ba motho a le mong ka mekotla ea polasetiki (29 × 18 × 13 cm) e nang le mealo ea cedr chip. Li ne li bolokiloe 14: lebone la 10: lebili le lefifi (mabone ho 0700 h) le ad libitum phihlello ea lijo le metsi. Mocheso o ne o bolokiloe ho 21 ± 1 ° C. Liphoofolo tsohle tse sebelisitsoeng thutong ena li ne li le pakeng tsa 90 le 120 matsatsi a lilemo. Liteko li entsoe ho latela tataiso ea Komiti ea Tlhokomelo ea liphoofolo le Ts'ebeliso Univesithing ea Florida State.

4.2. Sebaka se khethiloeng sa paradigm ea sebaka

Lisebelisoa tsa CPP li ne li ts'oana le se neng se hlalositsoe pele ebile se e-na le mabokose a mabeli a polasetiki a neng a bonahala ka mokhoa o fapaneng (o mosoeu le o mosoeu) mme a hokahantsoe ke phubu (hollow)Aragona et al., 2007; Liu et al., 2010). Re sebelisitse paradigm e nang le maemo e ntlafalitsoeng haufinyane li-voes tsa banna ba rorisang (Liu et al., 2010). Ka bokhutšoanyane, lithuto tsohle li ile tsa fuoa tlhahlobo ea 30 ea pele ho letsatsi ka 1 mme nako ea nako e sebelisitsoeng khorong ka 'ngoe e ile ea hlakoloa. Cage eo ho eona motho a ileng a qeta nako e nyane nakong ea tlhahlobo ea pele ho nako e ile ea khethoa e le koena e kengoang ka lithethefatsi 'me e' ngoe e khethiloe e le khetsi e nang le morara. Boemo bo etsahetse nakong ea metsotso e 'meli ea 40 letsatsi le leng le le leng ka matsatsi a mararo a latelang (matsatsi a 2-4). Nakong ea lithuto tsa hoseng (0900 h) lithuto li fumane liente tsa intša tsa 0.0, 0.1, 0.2, kapa 1.0 mg / kg d-AMPH sulfate (Sigma, St. Louis, MO, USA) e qhibilihile ka saline, hang pele e beoa ka sehokelong sa lithethefatsi. Nakong ea mananeo a thapama (1500 h), lithuto li ile tsa fumana ente ea saline hang-hang pele e kenngoa ka sakeng e kentsoeng letsoai. Teko ena e 'meli ka lenane la koetliso ea letsatsi e sebelisitsoe ho litoeba (Campbell le Spear, 1999; Zhou et al., 2010) hape e sebelisitsoe thutong ea rona e fetileng lithutong tsa basali tsa basali (Liu et al., 2010). Ntle le moo, paradigm ena e ile ea khethoa hobane data ea sefofane sa rona e bonts'itse phapang ea boitšoaro lipakeng tsa lithuto tse sa ts'oaroeng ka ente / li-paradigms tse sa fetoheng (tlhaiso e sa phatlalatsoang) le hobane litekanyetso tse hlophisitsoeng tsa kemiso le lisele tsa 'mele li ne li bohlokoa bakeng sa tekanyo ea polelo ea letšoao la DA litekong tse latelang hammoho le papiso e tobileng le datha tse tsoang ho banna prairie voles (Liu et al., 2010). Letsatsing la 5, lithuto tsohle li ile tsa lekoa bakeng sa boteng ba CPP tlhahlobisong ea metsotso ea 30. Palo eo liphoofolo li neng li tšela lipakeng tsa koekoe e tlalehiloe nakong ea tlhahlobo ea pele le ea kamora 'me e sebelisoa joalo ka leseli la ketsahalo ea entomotor.

4.3. Ho lokisa litonki

Likarolo li ile tsa hlakoloa ka potlako metsotso ea 30 kamora ho kenngoa ka ente ho liteko tsa liteko tsa 2 le 24 h ho latela jekete ea ho qetela ea liteko tsa liteko tsa liteko tsa 3 le 4. Mehopolo ea bona e ile ea tlosoa kapele mme hang-hang ea hoamisoa leqhoeng le omileng, pele e bolokoa ho −80 ° C. Li-Brains tse tsoang ho Teko ea 2 li ne li arotsoe ka mokhoa oa coronally ho 300 μm mme likarolo li ne li tsitsitsoe ka Superfrost / plus slide. Palesa ea bongo ea Paxinos le Watson (Paxinos le Watson, 1998) e sebelisitsoe ho supa libaka tse fapaneng tsa boko, ho kenyeletsoa le PFC (Plates 8-10), NAcc (Plates 9-11), CP (Plates 10-12) and VTA (Plates 40-43), moo lithaelese tse peli tsa methapo ea methapo li Bophara ba 1 mm bo nkiloe (Setšoantšo sa 2A) hape e bolokiloe ho −80 ° C ho fihlela e sebetsoa. Le ha e ne e se tikoloho ea boko ba mesocorticolimbic, CP e kenyellelitsoe ho tlhahlobo ea rona hobane eona, joalo ka NAcc le PFC, e amohela tlhahiso ea DAergic ho tsoa ho VTA (Maobane le Halliday, 1987) empa ho bonahala a sa kopanele taolong ea DAergic ea moralo oa khetho ea molekane oa li-commirie vole (Aragona et al., 2003, 2006; Liu le Wang, 2003). Bakeng sa Tlhahlobo ea 3 le 4, masapo a kelello a ne a khaoloa ka mokhoa o hlophisitsoeng ho likarolo tsa 10 tsa likarolo tsa 14 μm tse neng li kentsoe ka har'a li-Superfrost / plus slide.

4.4. Tlhatlhobo ea DA le tlhahlobo ea HPLC-ECD

Tlhopho ea DA e entsoe joalo ka ha ho hlalositsoe pele (Aragona et al., 2002), ntle le hore sampole ea tishu e ne e hlahisitsoe ho 50 μL ea 0.1 M perchloric acid e nang le 0.02% EDTA. Ts'isinyo ea DA e ile ea hlahlojoa e sebelisa ts'ebetso e phahameng ea metsi chromatography ka ho khetholloa hoa motlakase (HPLC-ECD) joalo ka ha ho hlalositsoe pele (Curtis et al., 2003) le mekhelo e latelang. Karolo ea mohala e ne e le 75 mM sodium dihydrogen phosphate monohydrate, 1.7 mM 1-octanesulfonic acid sodium letsoai, 0.01% triethylamine, 25 um EDTA, le 7% acetonitrile mme pH e ile ea fetoloa hore e be 3.0 le 85 phos. Sekhahla sa ho phalla e ne e le 0.5 ml / min. Sebaka se tloaelehileng sa li-curve le tlhoro e ile ea baloa joalo ka se hlalositsoeng peleAragona et al., 2003). Moeli oa ho lemoha e ne e le ~ 10 pg ka mohlala.

4.5. Ho hybridization ea D1 le D2 receptor mRNA

Likarolo tse ling tsa likarolo tsa boko ho tsoa ho liteko tsa 3 li ile tsa sebetsoa in situ lebasetere la lebasetere la DA receptor mRNA. Antisense and sense riboprobes (e fanoe ka seatla se bulehileng ke Dr. O. Civelli Univesithing ea California, Irvine, CA), e sebelisitsoe ho ngola D1 le D2 receptor mRNA ebile e lokiselitsoe joalo ka ha ho hlalositsoe pele (Liu et al., 2010). Likhetho li ngotsoe ka bonngoe ho 37 ° C bakeng sa 1 h ho buffer e ntlafalitsoeng e ngotsoeng e nang le 0.5 μg / μl ea template ea DNA e amehang, [35S] -CTP, 4 mM ea ATP, UTP, le GTP, 0.2 M dithiothreitol (DTT), RNasin (40 U / μl), le RNA polymerase (20 U / μl). Template ea DNA e ile ea siloa ka 1 U / μl DNaseI. Likhetho li ile tsa hloekisoa ho sebelisoa li-Columns tsa Chromatography (Bio-Rad, Hercules, CA) ebe li hlapolloa ka buffer ea hybridization e nang le 50% deionized formamide, 10% dextran sulfate, 3 × SSC, 10 mM sodium phosphate buffer (PB, pH 7.4), 1 Tharollo ea Denhardt, 0.2 mg / ml ea tomoso tRNA, le 10 mM DTT ho fana ka 5 × 106 cpm / ml.

Likarolo tsa methapo e ne e behiloe ho 4% paraformaldehyde ho 0.1 M phosphate buffered saline (PBS) ho 4 ° C bakeng sa 20 min, e hlotsoe ka PBS bakeng sa 10 min, mme e alafshoa ka 0.25% acetic anhydride ho triethanolamine (pH 8.0) bakeng sa 15 e sa tlamang. Joale li-Slide li ne li hlatsuoa ka 2 × saline sodium citrate (SSC), e entsoe metsi ka ho eketsa likhakanyo tsa ethanol (ETOH) (70, 95, le 100%) le moea o omisitsoeng.

Seketso se seng le se seng se fumane 100 μl solution ea hybridization e nang le se loketseng 35Probe e ngotsoeng lebitso-S, e ile ea koaheloa ka sekhukhu, ea ba ea kenngoa 55 ° C ka kamoreng e nang le mongobo bosiu bohle. Kamora ho kenella, li-Cover-Slips li tlositsoe ho 2 × SSC, li-slide li ile tsa hlatsuoa habeli ho 2 × SSC bakeng sa 5 min ebe li hlatsoa 37 ° C bakeng sa 1 h ho RNase buffer (8 mM Tris-HCl, 0.8 mM EDTA, le 0.4 M NaCl, pH 8.0) e nang le 25 mg / ml RNaseA. Ka mor'a moo, li-slide li ile tsa hlatsuoa ka ho fokotseha ho tsepamisoa ha SSC (2 × SSC, 1 × SSC, le 0.5 × SSC) bakeng sa 5 min e 'ngoe le e' ngoe 'me e ne e kentsoe 0.1 × SSC ho 65 ° C bakeng sa 60 ° C bakeng sa 1 °. Kamora nako, li-slide li ile tsa tlisoa mochesong oa kamore, tsa fokotsoa ke metsi ka lebaka la ho eketseha ha li-ETOH, le ho omisoa ke moea. Likarolo li ile tsa kenngoa filimi ea BioMax MR (Kodak, Rochester, NY) bakeng sa linako tse fapaneng, ho latela probe le sebaka sa thahasello, ho hlahisa li-autoradiogram tse nepahetseng. Bakeng sa NAcc le CP, D2R le D14R mRNA likarolo tse ngolisitsoeng li ile tsa kenngoa filimi bakeng sa 60 le 1 h, ka ho latellana, ha likarolo tse ngolisitsoeng bakeng sa D2-like le D15-like receptor binding li ne li qetetse 6.5 le 2 h, ka ho latellana. Bakeng sa VTA, likarolo tse ngotsoeng bakeng sa D60R mRNA li ile tsa qaptjoa bakeng sa 2 h mme tse ngolisitsoeng bakeng sa tlama-joaloka D40 li ne li qetetse XNUMX h. Matla a taolo ea RNA a ile a boela a lekoa bakeng sa phuputso e 'ngoe le e' ngoe 'me ha a ka a ngolloa lebitso, joalokaha ho ne ho lebelletsoe.

4.6. Boitsebiso bo ikemetseng ba DA receptor

Bakeng sa Teko ea 4, likarolo tse ling tsa likarolo tsa boko li ile tsa sebetsoa bakeng sa D1-like le D2-like receptor autoradiography. Le ligand-like D1 [125I] SCH23982 le ligand-D2-ligand [125I] 2'-iodospiperone e fumanoe ho PerkinElmer (Waltham, MA). DA receptor autoradiography e entsoe joalo ka ha ho hlalositsoe pele (Aragona et al., 2006).

4.7. Tlhahlobo ea lintlha

Bakeng sa Teko ea 1, CPP e hlalositsoe ke keketseho e kholo ea nako e sebelisitsoeng terakeng e entsoeng ka lithethefatsi nakong ea liteko tsa morao-rao ha e bapisoa le teko ea pele, joalo ka ha e lekantsoe ke paired t-etona. Ketsahalo ea locomotor e ile ea hlahlojoa ho sebelisoa mehato e 'meli e pheta-phetoang ANOVA ha e bapisoa le tlhahlobo ea kamora' tlhahlobo (ka har'a taba) le phapang ea maikutlo ka kalafo (lipakeng tsa taba-e fapaneng). Bakeng sa Teko ea 2, tšubuhlellano ea DA ea sampuli e ngoe le e ngoe e ne e etselitsoe maemo a tloaelehileng ho sebelisa protheine e phethahetseng ea sampole eo ho laola boholo ba lithane tse bokelletsoeng. Boleng bo tloaelehileng ba khatello ea DA (pg / μg tishu) bo ile ba fetoloa liperesente tsa mofuta oa DA oa taolo ea letsoai. Sebakeng se seng le se seng sa boko, karolo ea DA lipakeng e ne e bapisoa le a t-etona. Ho liteko tsa 3 le 4, li-autoradiogram li ile tsa hlahlojoa bakeng sa methapo ea mahlo ea ho ngolla kapa ho amohela li-receptor ho NAcc, CP le VTA ba sebelisa lenaneo la litšoantšo tsa k'homphieutha (NIH IMAGE 1.60) (PFC e sa kenyelletsoa tlhahlobisong kaha sebaka sena se sa bonts'e karabelo. ho kalafo ea AMPH ho Teko ea 2). Boemo ba rostral / caudal ba tlhahlobo ea litšoantšo bakeng sa NAcc, CP le VTA li ne li tšoana hantle le kamoo ho hlalositsoeng Teko ea 2. Phapang ea Neuroanatomical pakeng tsa NAcc le CP e entsoe ho sebelisa Paxinos le Watson rat brain atlas (Paxinos le Watson, 1998) e le tataiso, e bonts'ang sebopeho sa mongolo le sebaka sa boitumelo ba ka ntle. Likarolo tsa karolo e 'ngoe le e' ngoe ea boko li ne li bapisoa ka tsela e fapaneng lipakeng tsa lithuto, 'me mekhoa ea motho ka mong ea thuto ka' ngoe e ne e fumanoa ka ho lekanya methapo ea methapo ea methapo likarolong tse tharo ho tsoa karolong ka 'ngoe ea boko ka phoofolo ka' ngoe. Botebo ba morao bo ne bo tlositsoe ho tekanyo ea karolo ka 'ngoe. Metsoako ea ho qetela ea mahlo e ile ea fetoloa ho ba liperesente tse ling tsa matla a taolo ea saline. Liphapang tsa sehlopha ho mRNA kapa maemong a tlamang bokong ba boko bo ile ba hlahlojoa bakeng sa receptor e 'ngoe le e' ngoe ea DA e sebelisa a t-etona. Boemo ba bohlokoa bo thehiloe ho p

lumela hore baa fokola

Re leboha Kevin Young le Adam Smith ka ho bala ha bona ho qaqileng ha buka e ngotsoeng ka letsoho. Mosebetsi ona o tšehelitsoe ke National Institutes of Health Grants DAF31-25570 ho KAY, MHF31-79600 ho KLG, le DAR01-19627, DAK02-23048, le MHR01-58616 ho ZXW.

Mongolo o botlaaseng ba leqephe

Likhaloso: AMPH, amphetamine; ANOVA, ho hlahlojoa ha phapang; CP, caudate putamen; CPP, sebaka se ratang maemo; DTT, dithiothreitol; DA, dopamine; ETOH, ethanol; HPLC, ts'ebetso e phahameng ea mokelikeli oa metsi; ip, intraperitoneal; PCF, medial preambilial cortex; NAcc, li-bokellus tsa li-nucleus; PBS, letsoai le fumanehang ka phofo; SSC, saline sodium citrate; PB, sodium phosphate buffer; VTA, sebaka se khubung ea moea

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