J Neurosci. 2011 Jun 8; 31 (23): 8625-33.
St Onge JR, Abhari H, Floresco SB.
mohloli o moholo
Lefapha la Psychology le Brain Center Center, Univesithi ea British Columbia, Vancouver, British Columbia V6T 1Z4, Canada
inahaneloang
Likhetho pakeng tsa meputso e itseng le e sa tsitsang ea boholo bo fapaneng bo lumetse ho kopanngoa ka bobeli lobes le tsamaiso ea mesocorticolimbic dopamine (DA). Litekong, manong a tšebetso a tšebetso ea DA kapa ho kenella ha medial prefrontal cortex (PFC) e sitisa ho nka liqeto mabapi le likotsi le meputso. Leha ho le joalo, ha ho hlake hore na phetisetso ea PFC DA e kenya letsoho joang lits'ebetsong tsena. Re rarolle bothata bona ka ho hlahloba litlamorao tsa ho ba makhopho a meriana ea D1 le li-receptor tsa D2 ho medial (prelimbic) PFC mabapi le khetho pakeng tsa meputso e menyenyane, e meholo, empa e le e makatsang. Likhoto li ile tsa koetlisetsoa mosebetsi oa ho fokotsa litheko moo ho nang le lever e le 'ngoe e ileng ea tlisa pellet e le' ngoe ka monyetla oa 100%, e 'ngoe ea tlisa li-pellets tse' ne, empa monyetla oa ho fumana moputso o fokotsehile ho feta lithibelo tsa liteko (100, 50, 25, 12.5%). D1 blockade (SCH23390) ho PFC ea moruo e fokotse khetho ea khetho e kholo / e kotsi. Ka lehlakoreng le leng, D2 blockade (eticlopride) e fokotsitse theolelo ea mohlomong le khetho e kotsi. SKF1 ea D81297 agonist e bakile keketseho e nyane, e sa rateheng ea khetho ea lever e kholo / e kotsi. Leha ho le joalo, D2 receptor stimulation (quinpirole) e bakile tšenyo ea 'nete ha ho etsoa liqeto, e tebisa karohanyo ea litheko le khetho e mpe ho tloha kapa ho ea ka khetho e kotsi ha e le ntle kapa e le menyetla e fokolang. Liphumano tsena li fana ka maikutlo a hore li-receptor tsa PFC D1 le D2 li etsa dissociable, leha ho le joalo li tlatsana, tlatsetso ho beha likotsi tsa kahlolo / moputso. Ka ho leka-lekanya lintho hantle pakeng tsa ts'ebetso ea li-receptor ea D1 / D2, DA e kanna ea thusa ho nchafatsa likahlolo tsena, ho khothaletsa tlhekefetso ea maemo a hona joale a matle kapa tlhahlobo ea ba nang le phaello e ngata ha maemo a fetoha.
Selelekela
Ho senyeha ha sistimi ea mesocorticolimbic dopamine (DA) ho hokahantsoe le likhaello tse tebileng ha ho etsoa liqeto tse amanang le mafu a itseng a kelello. Tsena li kenyelletsa batho ba nang le schizophrenia (Hutton et al., 2002), lefu la Parkinson (Pagonabarraga et al., 2007), le bokhoba ba lithethefatsi (Rogers et al., 1999). Mefuta ea liphoofolo ea ho etsa liqeto e senotse hore lits'ebetso tsa phetisetso ea DA li ka fetola likhetho pakeng tsa tse nyane, tse fumanehang habonolo, le meputso e meholo empa e le theko e phahameng. Thibelo e hlophisehileng ea li-receptor tsa D1 kapa D2 e fokotsa khetho ea ho ema nako e teletsana kapa ho sebetsa ka thata ho fumana moputso o moholo, athe phetiso ea DA e eketsang e na le litlamorao tse fapaneng boitekong-kapa ho liehiseng ho etsa liqeto, ho eketsa kapa ho fokotsa khetho ea meputso e meholo e tlisoang ke Litsenyehelo tse kholo (Cousins et al., 1994; Cardinal et al., 2000; Denk et al., 2005; van Gaalen et al., 2006; Floresco et al., 2008a; Bardgett et al., 2009). Ka mokhoa o ts'oanang, ha likhoto li khetha lipakeng tsa meputso e nyane, e itseng le e kholo, empa e le kotsi bakeng sa mosebetsi oa ho fokotsa litheko, tsamaiso ea methapo ea D1 kapa D2 antagonists e fokotsa khetho bakeng sa likhetho tse kholo, tse kotsi (St. Onge le Floresco, 2009). Ka lehlakoreng le leng, li-agonists tsa D1 kapa tsa D2 li khetha khetho e nepahetseng ka likhetho tse kholo le tse kotsi. Leha ho le joalo, ka lebaka la hore libaka tse ngata tsa boko li kentsoe ts'ebetsong ea likotsi tsa meputso / moputso (mohlala, li-lobes tse ka pele, li-ventral striatum, amygdala) (Floresco et al., 2008b), libaka tse DA e ka etsang ts'ebetso ea tsona ho susumetsa lits'ebetso tsena li lula li sa hlaka .
DA e fetolela mesebetsi e mengata ea kelello e kopantsoeng ke libaka tse fapaneng tsa preortal cortex (PFC), joalo ka boitšoaro bo feto-fetohang, mohopolo oa ho sebetsa, le lits'ebetso tsa tlhokomelo (Williams le Goldman-Rakic, 1995; Granon et al., 2000; Chudasama le Robbins, 2004; Floresco et al., 2006), hangata sebakeng se kentsoeng "U inverated U", moo mesebetsi e nyane haholo kapa e ngata haholo ea DA e sitisang mesebetsi e meng ea bolaoli. Leha ho le joalo, ho bile le lithuto tse fokolang tse hakanyetsang tlatsetso ea phetisetso ea PFC DA mefuteng e fapaneng ea ho etsa liqeto ka theko / melemo. Ho fokotsa ts'ebetso ea DA ho li-maamuzi tsa anterior cingate alters tse thehiloeng hodima liteko (Schweimer et al., 2005; Schweimer and Hauber, 2006), athe blockade kapa ho tsosa li-receptors tsa makhopho a PFC D1 li fokotsa khetho ea meputso e meholo, e lietsitsoeng (Loos et al., 2010 ). Haholoholo, ha ho na lipatlisiso tse entseng lipatlisiso tsa tlatsetso ea li-receptor tse fapaneng tsa PFC DA ho etsa liqeto tse behiloeng kotsing.
Mosebetsi oa morao-rao o bontšitse PFC ea prelimbic medial e le sebaka se mahlonoko molemong oa ho theola litheko tsa phenabilistic, athe tšebetso maemong a mang a marang-rang (anterior cingulate, orbitof Pambal, insular) ha e bonahale e kenya letsoho ts'ebetsong ena (St. Onge le Floresco, 2010). Ho qaptjoa ha PFC ea moruo ho ile ha eketsa khetho ea meputso e meholo, e makatsang ha menyetla ea ho e fumana e fokotseha ka nako e itseng, empa e fokotse khetho ha menyetla ea meputso e eketseha ka nako e telele. Liphetho tsa thuto ena li re lebisitse ho etsa qeto ea hore PFC ea moruo e sebeletsa ho hokahanya tlhahisoleseling mabapi le ho fetola menyetla ea meputso ho ntlafatsa litlhahiso tsa boleng tse etsang hore ho be bonolo ho etsa liqeto. Kaha o na le karolo ea bohlokoa eo micocortical DA e e bapalang ka mekhoa e meng ea ho utloisisa (Floresco le Magyar, 2006), thuto e teng hona joale e fuputse tlatsetso ea ts'ebetso ea pele ea D1 / D2 receptor mosebetsing oa ho etsa liqeto tse thehiloeng kotsing ka ho sebelisa mosebetsi oa ho theola.
Lisebelisoa le mekhoa
Liphoofolo.
Likhoto tsa banna tsa Long-Evans (Charles River Laboratories) tse boima ba 275-300 g qalong ea koetliso ea boits'oaro li sebelisitsoe bakeng sa teko. Ha li fihla, likhoto li ile tsa fuoa beke ea 1 ho tloaelana le kolone mme lijo li ne li lekantsoe ho 85-90% ea boima ba tsona ba ho fepa mahala bekeng e ngoe pele ho koetliso ea boits'oaro. Likhoto li ile tsa fuoa phihlello ea ho fumana metsi nakong ea teko. Ho fepa ho etsahetse malapeng a likhoto qetellong ea letsatsi la liteko, 'me boima ba' mele bo ne bo beiloe leihlo letsatsi le leng le le leng ho netefatsa ho theola boima ba 'mele nakong ea thibelo ea lijo le tlhokomelo kapa boima ba' mele bakeng sa liteko tse ling kaofela. Liteko tsohle li ne li le ho latela Lekhotla la Canada la Tlhokomelo ea Liphoofolo le Komiti ea Tlhokomelo ea Liphoofolo ea Univesithi ea British Columbia.
Lisebelisoa.
Teko ea boitšoaro e ile ea etsoa likamoreng tsa basebetsi tsa 12 (30.5 × 24 × 21 cm; Med Associates) e kentsoeng ka mabokoseng a nang le molumo, e mong le e mong a e-na le fan ho fana ka moea o pholileng le ho etsa lerata le leholo. Kamore e 'ngoe le e' ngoe e ne e kentsoe mekotla e 'meli e ka huloang, e' ngoe e le ka lehlakoreng le leng la kamohelo ea lijo moo ho matlafatsoang lijo (45 mg; Bio-serv) e neng e tsamaisoa ka motlakase. Likamore li ne li boneselitsoe ke lebone le le leng la ntlo la 100 mA le neng le le kahare-holimo leboteng le shebaneng le ba bonojoana. Ho ne ho behiloe lifolakha tse 'ne tsa sephiri ka mahlakoreng a kamore ka' ngoe. Ketsahalo ea locomotor e bontšitsoe ke linomoro tsa likhefu tsa Photobeam tse etsahetseng nakong ea thuto. Lintlha tsohle tsa liteko li tlalehiloe ke komporo ea motho ea IBM e hokahaneng likamoreng ka sehokelo.
Koetliso e hatisang.
Li-protocol tsa rona tsa pele tsa koetliso li ne li ts'oana le tsa St. Onge le Floresco (2009), joalo ka ha li fetotsoe ho tsoa ho Cardinal et al. (2000). Letsatsing la pele ba pepesetsoa likamoreng, likhoto li ile tsa fuoa li-pellets tsa tsoekere tsa ∼25 tsoaneng ea bona. Letsatsing la pele la thupelo, li-pellets tsa 2-3 li ile tsa kenngoa ka senoelong sa lijo 'me li-pellets tse sithabetseng tsa beoa ho lever pele phoofolo e kenngoa ka phapusing. Likhoto li ile tsa koetlisoa pele tlasa kemiso ea 1 e tsitsitseng ea 60 mochini oa 30 min, pele bakeng sa lever e le 'ngoe,' me ea phetoa bakeng sa lever e 'ngoe (tse loantšang le letšehali / le letona pakeng tsa lithuto). Likhoto li ile tsa koetlisoa molemong oa mosebetsi o felletseng. Linako tsena tsa teko ea 90 li qalile ka hore ba-levers ba khutlisetsoe le kamore e sebetsang lefifing. Nako le nako ha 40 s, ho ile ha qaloa nyeoe ka leseli la ntlo le ho kenngoa ha e 'ngoe ea likhetla tse peli ka phapusing. Haeba rat e ne e sa khone ho araba mokoloto o ka har'a 10 s, lever e ne e huloa hape, kamore e fifetse, 'me nyeoe e ne e fuoe nyeoe. Haeba lenane le arabile ka har'a 10 s, lenti le ile la khutlisoa mme pellet e le 'ngoe ea tlisoa ka monyetla oa 50%. Mokhoa ona o ne o sebelisoa ho tloaetsa litoeba ka mofuta oa mosebetsi o felletseng. Tekong e 'ngoe le e' ngoe ea liteko, lever ea letsoho le letšehali kapa le letona e ile ea hlahisoa hang, 'me taelo kahare ho liteko tse peli e ile ea fanoa ka tšohanyetso. Liroto li ile tsa koetlisetsoa N5-6 d ho ea ka mokhoa oa 80 kapa liteko tse atlehileng (ke hore; ≤10 omissions).
Mosebetsi oa ho fokotsa litheolelo.
Mosebetsi oa mantlha o sebelisitsoeng lithutong tsena o hlalositsoe pele (Floresco le Whelan, 2009; Ghods-Sharifi et al., 2009; St. Onge le Floresco, 2009, 2010; St. Onge et al., 2010), mme e ne e fetotsoe ho tloha ho se hlalositsoeng ke Cardinal le Howes (2005) (sa feiga. 1). Ka bokhutšoanyane, likhoto li amohetse likarolo tsa letsatsi le letsatsi tse nang le liteko tsa 72, tse arohaneng le li-block tsa 4 tsa liteko tsa 18. Seboka sohle se ile sa nka metsotso ea 48 ho phethela, 'me liphoofolo li ile tsa koetlisoa 6-7 d ka beke. Seboka se qalile lefifing ka bobeli ba levers ba khutliselitsoeng (boemo ba maikutlo). Nyeoe e qalile ka nako e 'ngoe le e' ngoe ea 40 ka khanya ea ntlo, 3 s hamorao, ho kenyelletsoa ka lehare kapa ka bobeli kamoreng (sebopeho sa teko e le 'ngoe se bonts'itsoe ho Fig. 1). Lever e le 'ngoe e ne e reretsoe lever e kholo / e kotsi, e ngoe e le lenala le lenyane / le itseng, le neng le lula le feto-fetoha ho pholletsa le thupelo (khahlanong le leqele / leqele). Haeba rat e ne e sa arabe ka ho tobetsa lever kahare ho 10 s ea lever, kamore eo e ne e ka fetoloa boemong ba lipakeng ho fihlela nyeoe e latelang (ho siea). Ha ho ne ho khethoa motho ea neng a etsa litšepe, ba ne ba khutla ka bobeli. Khetho ea lever e nyane / e itseng e ne e lula e fana ka pellet e le 'ngoe ka monyetla oa 100%; khetho ea lever e kholo / e kotsi e tlisitsoeng ke li-pellets tsa 4 empa ka monyetla o itseng. Ha lijo li tlisoa, leseli la ntlo le ile la sala le le leng la 4 s ka mor'a hore karabelo e etsoe, kamora hore kamore e khutlele seterekeng. Li-pellets tse ngata li ile tsa tsamaisoa ka 0.5 s ka thoko. Li-block tsa 4 li ne li entsoe ka liteko tsa khetho tsa 8 tseo ho tsona ho ileng ha hlahisoa lever e le 'ngoe (liteko tsa 4 bakeng sa mokopuli e mong le e mong, e hlophisitsoeng ka bobeli ka bobeli), e lumellang liphoofolo ho ithuta ka monyetla oa ho fumana moputso o moholo kapa o monyane ho thibela e ngoe le e ngoe. Sena se ile sa lateloa ke liteko tsa mahala tsa khetho tsa 10, tseo ho tsona ho neng ho hlahisoa levers ka bobeli ebe phoofolo e khetha e nyane / e itseng kapa e kholo kapa e kotsi. Monyetla oa ho fumana li-pellets tsa 4 kamora ho tobetsa lever e kholo / e kotsi e arohaneng ho li-block: qalong e ne e le 100%, ebe 50%, 25%, le 12.5%, ka ho latellana, bakeng sa boloko bo bong le bo bong bo latellanang. Monyetla oa ho fumana moputso o moholo tekong e 'ngoe le e' ngoe o hlahisitsoe ho tsoa ho se behiloeng mohlomong. U sebelisa menyetla ena, khetho ea lere e kholo / e kotsi e ka ba molemo litsing tse peli tsa pele, mme ea ba kotsi sebakeng sa ho qetela, athe likhoto li ka fumana palo e lekanang ea li-pellets tsa lijo kamora ho araba ka lever nakong ea thibelo ea 25%. Ka hona, maemong a mararo a ho qetela a liteko tsa mosebetsi ona, khetho ea meputso e meholo e na le "kotsi" ea ho se fumane moputso tekong e filoeng. Litekanyetso tsa ho qala khetho le ts'ebetso e akaretsang ea locomotor (likhefu tsa photobeam) le tsona li tlalehiloe. Liroto li koetliselitsoe mosebetsi ho fihlela, e le sehlopha, bona (1) ba khethile lever e kholo / e kotsi nakong ea teko ea pele (100% mohlomong) bonyane 80% ea liteko tse atlehileng, mme (2) e bonts'a maemo a tsitsitseng a motheo khetho, e lekiloeng ho sebelisa mokhoa o ts'oanang le o hlalositsoeng ke Winstanley et al. (2005) le St. Onge le Floresco (2009). Ka bokhutšoanyane, tlhaiso-leseling e tsoang likarolong tse tharo tse latellanang e ile ea hlahlojoa ka mehato e pheta-phetoang ANOVA e nang le lintlha tse peli tse kahare (letsatsi le thibelo).
Setšoantšo sa 1.
Moralo oa mosebetsi. Lits'enyehelo / melemo ea melemo / melemo e amanang le ho arabela ho lever (A) le sebopeho sa teko e le 'ngoe ea khetho ea mahala (B) mosebetsing oa ho fokotsa litheko.
Mosebetsi oa khethollo ea boholo ba ona.
Joalo ka ha re entse pejana (Ghods-Sharifi et al., 2009; Stopper and Floresco, 2011), re ile ra etsa qeto ea mantlha ea hore haeba kalafo e itseng e fokotseha ho khetheha bakeng sa lever e kholo / e kotsing ea ts'ebetso ea ho fokotsa litheko, lihlopha tse arohaneng tsa liphoofolo ba tla koetlisoa ba be ba lekoe mosebetsing oa khethollo ea boholo ba ho bona hore na phello e bakiloe ke ho senyeha ha khethollo lipakeng tsa meputso e amanang le meputso e 'meli. Litekong tsena, likhoto li ile tsa koetlisetsoa ho hatisa levers tse ka etsoang ha ho ntse ho etsoa mosebetsi oa ho fokotsa litheko, kamora moo ba koetlisetsoa mosebetsi oa khethollo. Mona, likhoto li ile tsa khetha pakeng tsa lever e le 'ngoe e tsamaisang pellet e le' ngoe e isang li-pellets tse 'ne. Meputso e meholo le e meholo e ile ea fanoa hang kamora karabelo e le 'ngoe ka monyetla oa 100%. Seboka se ne se e-na le lithibelo tse 'ne tsa liteko,' me e 'ngoe le e' ngoe e na le 2 e neng e tlameha ho khetha le ho latela khetho ea 10.
Phekolo.
Likhoto li ile tsa etsoa opereishene hang ha sehlopha se bonts'a mekhoa e tsitsitseng ea khetho bakeng sa matsatsi a 3 a latellanang. Kamora hore ho be le tlhahlobo ea botsitso, likhoto li ile tsa fuoa lijo tsa lipapatso mme, 2 d hamorao, tsa etsoa opereishene ea methapo. Likhoto li ne li sa anngoe ka 100 mg / kg ketamine hydrochloride le 7 mg / kg xylazine mme kamora moo li kenngoa ka li-bilateral 23 gauge stainless tataiso ea tšepe ea cannulae sebakeng sa prelimbic sa Dial PFC (sede e sephara; anteroposterior, + 3.4 mm; medial-lateral 0.7 mm ho tloha bregma; le dorsoventral, −2.8 mm ho tloha dura). Li-obdurator tse mashome a mararo tsa pampiri, tse bonojoana le qetellong ea cannulae ea tataiso, li ile tsa lula li le teng ho fihlela infusions e etsoa. Liroto li ile tsa fuoa bonyane 7 d ho hlaphoheloa opereisheneng pele ho liteko. Nakong ena ea ho hlaphoheloa, liphoofolo li ne li tsamaisoa bonyane 5 min letsatsi le leng le le leng 'me lijo li ne li lumelloa ho 85% ea boima ba bona ba ho fepa mahala. Boima ba 'mele bo ne bo behiloe leihlo khafetsa letsatsi le leng le le leng ho netefatsa ho theola boima ba' mele ka nako ena.
Protocol ea Microinfusion.
Kamora ho hlaphoheloa opereisheneng, likhoto li ile tsa khutlisoa ka leqheka la ho khetholloa kapa ho khetholla boholo ba mosebetsi oa 5 d mme, e le sehlopha, ba bonts'a maemo a ikhethileng a boits'oaro. Bakeng sa 3 d pele ho letsatsi la teko ea micinfusion ea pele, li-obdurator li ile tsa tlosoa mme ts'ebetso ea ts'ebetso ea mock ea tsamaisoa. Li-injection tsa tšepe tse se nang tšepe li ile tsa kenngoa ka har'a cannulae ea li-2 min, empa ha ho na ts'ebetso e ileng ea etsahala. Mokhoa ona o ne o tloaetse litoeba ho tloaelo ea infusions ho fokotsa khatello ea maikutlo matsatsing a latelang a liteko. Letsatsi ka mor'a ho bonts'a litheko tse tsitsitseng, sehlopha se amohetse letsatsi la eona la pele la tlhahlobo ea microinfusion.
Moralo oa lithuto tse ka hare o ile oa sebelisoa bakeng sa liteko tsohle. Lithethefatsi tse latelang li sebelisitsoe: D1 antagonist R - (+) - SCH23390 hydrochloride (1.0 μg, 0.1 μg; Sigma-Aldrich), D2 antagonist eticlopride hydrochloride (1.0 μg, 0.1 μg DugNGXNGXG GXUMX GμUMX μgX, GNUMX μg, GNUMX μg; SKF1 (81297 μg, 0.4 μg; Tocris Bioscience), le D0.1 agonist quinpirole (2 μg, 10 μg; Sigma-Aldrich). Lithethefatsi tsohle li ile tsa qhibiliha ho saline ea 'mele ea 1%, ea kenngoa ho fihlela e qhibiliha, le ho sireletsoa leseling. Lidao tse khethiloeng kaofela li ngotsoe hantle ke sehlopha sa rona le ba bang ho ba le boitšoaro ha ba fuoa intracerebrally (Seamans et al., 0.9; Ragozzino, 1998; Chudasama le Robbins, 2002; Floresco le Magyar, 2004; Floresco et al. 2006; Haluk le Floresco, 2006; Loos et al., 2009).
Litlhaselo tsa bahanyetsi ba D1 le D2, agonists, le saline li ne li tsamaisoa habeli ka har'a PFC ea moriana ka pompo e nang le microsyringe e hokahantsoeng le lefuba la PE le 30 gauge cannulae e bontšitseng 0.8 mm nakong ea pheletso ea tataiso, ka tekanyo ea 0.5 μl / 75 s. Innng cannulae e ile ea siuoa sebakeng sa metsotso e meng ea 1 ho lumella phapang. Rate e 'ngoe le e' ngoe e lutse ka har'a ntlo ea eona ea lehae ea 10 min pele ho liteko tsa boitšoaro.
Ho sebelisitsoe lihlopha tse 'ne tse arohaneng tsa likhoto ho leka litlamorao tsa metsoako e mene (mohanyetsi oa D1, mohanyetsi oa D2, D1 agonist, D2 agonist). Taelo ea kalafo (letsoai, lethal dose, lethal dose e phahameng) e ne e bapisoa le likhoto kahare ho sehlopha se itseng sa kalafo. Kamora letsatsi la pele la tlhahlobo ea infusion, likhoto li ile tsa fumana letsatsi la mantlha la koetliso (ha ho na infusion). Haeba, bakeng sa rat e le ngoe, khetho ea lever e kholo / e kotsi letsatsing lena e khelohile ke> 15% ho tloha qalong ea eona ea preinfusion, rat e fumane letsatsi le leng la koetliso pele ho tlhahlobo ea bobeli ea infusion. Letsatsing le hlahlamang, likhoto li ile tsa fuoa infusion ea bobeli e sa lekanyetsoang, ea lateloa ke letsatsi le leng la mantlha, mme qetellong ea tšeloa.
Bohlale.
Kamora ho qeta tlhahlobo eohle ea boitsoaro, likhoto li ile tsa bolaoa ka phapusing ea khabone ea khabone. Li-brains li ile tsa tlosoa 'me tsa kenngoa ka tharollo ea 4% formalin. Mabili a ne a hoamme le ho qaqisoa ka likarolo tsa 50 μm pele a ts'oaroa le ho hloekisoa ka cresyl violet. Meetso e ile ea netefatsoa ka ho bua ka atlas ea neuroanatomical ea Paxinos le Watson (1998). Libaka tsa infusions tse amohelehang ho PFC ea moruo li hlahisoa ka liphanele tse nepahetseng tsa Setšoantšo sa 2.
Setšoantšo sa 2.
Bohlale. Schematic ea likarolo tsa coronal tsa boko ba rat e bonts'a libaka tse ngata tse amohelehang tsa infusions ka boemo ba rostral-caudal ba PFC ea methapo bakeng sa likhoto tsohle.
Tlhahlobo ea lintlha.
Mokhahlelo o ka sehloohong oa lithahasello e ne e le liperesente tsa likhetho tse lebisitsoeng ho lever e kholo / e kotsi bakeng sa teko e ngoe le e ngoe ea liteko tsa khetho ea bolokolohi, e hlophisang liphoso tsa liteko. Bakeng sa block e ngoe le e ngoe, sena se baliloe ka ho arola palo ea likhetho tsa lever e kholo / e kotsi ka palo ea liteko tse atlehileng. Lintlha tse ikhethileng bakeng sa sehlopha ka seng sa lithethefatsi li ile tsa hlahlojoa ho sebelisoa li-ANOVA tse peli, ka kalafo (letsoai, tekanyetso e tlase, tekanyetso e phahameng) le teko ea liteko (100, 50, 25, 12.5%) e le lisosa tsa kahare ho sehlooho. Phello ea mantlha ea block bakeng sa data ea khetho e ne e le bohlokoa litekong tsohle tsa litheolelo (p <0.05), ho bonts'a hore likhoto li theoletse khetho ea lever e kholo / e kotsi joalo ka ha monyetla oa moputso o moholo o fetotsoe ho li-block tse nne. Phello ena e ke ke ea boleloa hape. Likarabo tsa likarabo, mesebetsi ea baetsi ba likoloi (likhechana tsa photobeam), le palo ea likheo tse lekiloeng li ile tsa hlahlojoa ka li-ANOVA tsa tsela e le 'ngoe.
Karolo e fetileng Karolong e latelang
Results
Lihlopheng tse 'ne tsa liphoofolo qalong li ile tsa koetlisetsoa liteko tse fapaneng tsa ba tsa abeloa sehlopha se le seng sa lithethefatsi. Lihlopheng tse peli tsa pele tsa 16 e 'ngoe le e' ngoe, e etselitsoeng liteko tsa bahanyetsi ba D1 le D2, e hloka tekanyo ea 28 d ea boikoetliso pele e fihlela ts'ebetso e tsitsitseng ea khetho le ho amohela liteko tse hanyetsanang tsa microinfusion. Lihlopha tse peli tsa bobeli tsa 14 le 14 rats bakeng sa D1 le li-agonists tsa D2 li hloka tekanyo ea 34 d ea boikoetliso pele e fihlela ts'ebetso e tsitsitseng ea khetho. Karolo ea karabelo, locomotor, le data ea ho siea teko e fumanoeng matsatsing a liteko bakeng sa lihlopha tsohle tse 'ne li hlahisoa ho Tafole 1.
Tafole 1.
Kameho, ho siea teko, le data ea morao-rao ea karabelo e fumanoeng kamora ho sebelisoa ha saline kapa lithethefatsi ho PFC ea moriana
D1 le D2 receptor antagonism le theolelo ea probabilistic
D1 blockade
Qalong, likhoto tse 16 li ile tsa koetlisetsoa teko ena. Phoofolo e le 'ngoe e ile ea shoa nakong ea ts'ebetso ea bongaka mme lintlha tse tsoang ho tse ling tse tharo li ile tsa tlosoa ka lebaka la ho beoa ka mokhoa o sa nepahalang, ho ileng ha fella ka ho qetela n = 12.Hlahlobo ea tlhaiso-leseling e senotse hore li-infusions tsa intra-PFC tsa mohanyetsi oa D1 SCH23390 li felletse ka tšusumetso e kholo ea kalafo (F (2,22) = 3.26, p = 0.05) empa ha ho na kalafo × block interaction (F (6,66) = 0.92, ns). Tekanyo e phahameng ea SCH23390 (1 μg) e fokolitse haholo khetho bakeng sa lever e kholo / e kotsi libakeng tse tharo tsa ho qetela (p <0.05; Setšoantšo sa 3A), athe tekanyetso e tlase (0.1 μg) ha e hlahise phetoho e ts'epahallong ea boits'oaro ba khetho. Thibelo ea D1 e ne e se na tšusumetso ho latency response (F (2,22) = 0.18, ns), ho tloheloa ha liteko (F (2,22) = 0.54, ns), kapa lipalo tsa locomotor (F (2,22) = 1.66, ns ).
Setšoantšo sa 3.
Liphello tsa mekhoa e meng ea ho amohela li-receptor tsa DA ho PFC e bohareng ka theolelo e ka bang teng. Lintlha li reriloe ho latela liperesente tsa khetho ea lever e kholo / e kotsi nakong ea liteko tsa khetho ea mahala ka monyetla oa block (x-axis). Matšoao a emela "SEM" e bolelang. Linaleli tse putsoa li supa tšusumetso e kholo ea mantlha (letsoai le tekanyetso e phahameng, p <0.05). Linaleli tse ntšo li bontša phapang e kholo (p <0.05) lipakeng tsa maemo a kalafo nakong ea monyetla o itseng oa thibelo. A, Infusions ea tekanyetso ea 1.0 μg ea mohanyetsi oa D1 SCH23390 e potlakisitse theolelo ea monyetla, ho fokotsa khetho e kotsi. B, Ka lehlakoreng le leng, infusions ea 1.0 μg dose ea D2 antagonist eticlopride e liehisitse litheolelo le khetho e eketsehileng ea likotsi. C, D1 agonist SKF81297 e bakile keketseho e nyane, e sa reng letho ea khetho e kotsi. D, Infusions ea 10 μg dose ea D2 agonist quinpirole e felisitse theolelo, e fokotsa khetho e kotsi nakong ea block ea pele le khetho e ntseng e eketseha nakong ea block ea ho qetela.
D2 blockade
Qalong, likhoto tse 16 li ile tsa koetlisetsoa teko ena. Phoofolo e le 'ngoe e ile ea shoa nakong ea opereishene mme tlhaiso-leseling e tsoang ho tse ling tse tharo e ile ea tlosoa ka lebaka la ho beoa ho sa nepahalang, ho ileng ha fella ka ho qetela n = 12.Hlahlobo ea tlhaiso-leseling e boetse e senotse tšusumetso e kholo ea kalafo (F (2,22) = 3.76, p <0.05) empa ha ho na kalafo × block interaction (F (6,66) = 0.84, ns). Leha ho le joalo, ho fapana le litlamorao tsa thibelo ea D1 receptor, tekanyetso e phahameng ea eticlopride (1 μg) e eketsehile haholo khetho bakeng sa lever e kholo / e kotsi ho li-block tsohle (p <0.05; Fig. 3B), e nang le lethal dose e tlase (0.1 μg ) ho hlahisa keketseho e nyane, empa e sa reng letho ea khetho. Eticlopride e ne e se na tšusumetso ho latency response (F (2,22) = 0.63, ns), ho tloheloa ha liteko (F (2,22) = 1.45, ns), kapa lipalo tsa locomotor (F (2,22) = 0.99, ns) . Kahoo, ho thibeloa ha li-receptor tsa D1 kapa D2 ho PFC e kahare ho bile le litlamorao tse khahlano le phokotso ea monyetla. Ho fokotsa ts'ebetso ea li-receptor tsa D1 ho ekelitse theolelo ea meputso e meholo, e sa tsitsang, athe lehloeo la D2 receptor le fokotsa theolelo, le bonahala le fokotseha le ho eketseha ka khetho e kotsi.
D1 le D2 receptor e tsitsitseng le theolelo ea probabilistic
Ts'usumetso ea D1
Pele, likhoto tsa 14 li ne li koetliselitsoe teko ena. Phoofolo e le 'ngoe e ile ea shoa nakong ea ts'ebetso ea opereishene mme data e tsoang ho rat e le' ngoe e ne e sa kenyelletsoe hobane lintlha tsa hae tsa mantlha tsa khetho e ne e le li-SDN tsa 2 ka tlase ho se boleloang ke sehlopha kaofela, ho fella ka n = 12 ea ho qetela. Kamora ho tsamaisoa ha D1 agonist SKF81297 ho moroto oa PFC, litoeba li bonts'a phello e fapaneng le e ts'oeroeng ke mohanyetsi oa D1, e bonts'a keketseho e lekanang ea khethollo bakeng sa lever e kholo / e kotsi, mme phello e ba kholo ka ho fetisisa kamora kalafo le tlaase, tekanyo ea 0.1 μg. Leha ho e-na le tloaelo ena, tlhahlobo ea tlhaiso-leseling ea khetho ha ea ka ea senola phello e kholo ea kalafo (F (2,22) = 2.05, ns) kapa kalafo ea ts'ebetso ea ho thibela (block block block (F (6,66) = 0.10, ns; Fig. 3C) papiso pakeng tsa maemo a tlase a lethal dose le kalafo ea saline e bontšitse tloaelo ho bohlokoa ba lipalo (p = 0.086). Agonist ea D1 le eona e ne e se na phello ho li-latency tsa ho arabela (F (2,22) = 0.67, ns), liqoso tsa linyeoe (F (2,22) = 0.06, ns), kapa lipalo tsa locomotor (F (2,22) = 0.36, ns).
Ts'usumetso ea D2
Hape, likhoto tse 14 li ile tsa koetlisetsoa teko ena. Lintlha tse tsoang ho rat e le 'ngoe li ile tsa qheleloa ka thoko hobane tlhaiso-leseling ea hae ea mantlha e ne e sa bonts'a litheolelo tse hlahelletseng kamora ho koetlisoa ha 34 d, ha lintlha tse mabapi le rat e' ngoe li ile tsa tlosoa ka lebaka la ho beoa ka nepo, ho fella ka n = 12 ea ho qetela sehlopheng sena. Kalafo e nang le D2 agonist quinpirole e bakile tšusumetso ho khetho e neng e ikhethile ha e bapisoa le e hlohlelletsoang ke mohanyetsi oa DA ea amohelang kapa D1 agonist. Tlhatlhobo ea tlhaiso-leseling e senotsoeng ha e na tšusumetso e kholo ea kalafo (F (2,22) = 0.05, ns), empa ho bile le kalafo ea bohlokoa x block interaction (F (6,66) = 2.33, p <0.05, Dunnett's p <0.05). Liphuputso tse bonolo tse ka sehlohlolong li bonts'itse hore, ha lethal dose e tlase (1 μg) ea quinpirole e ne e sena phello boikhethelong, lethal dose le phahameng (10 μg) le hlahisitse phatlalatso ea "ho batalatsa" ea lekhalo la theolelo. Ka ho khetheha, tekanyetso ena haholo (p <0.05) e ile ea fokotsa khetho ea lever e kholo / e kotsi ho 100% block ea pele, empa ea eketsa khetho e kotsi nakong ea block ea ho qetela (12.5%) e amanang le infusions ea saline (Setšoantšo sa 3D). Ho feta moo, kamora ho ts'oaetsoa ke letsoai kapa 1.0 μg lethal dose ea quinpirole, likhoto li bontšitse theolelo e kholo ea khetho e kholo / e kotsi ha menyetla ea ho fumana moputso o moholo e fokotsehile nakong ea thuto (p <0.005). Ka lehlakoreng le leng, karolo ea khetho ea khetho ena ha ea ka ea fetoha haholo ho li-block tse nne kamora kalafo ka 10 μg ea quinpirole (p> 0.25). Quinpirole e ne e se na tšusumetso ho tlolo ea liteko (F (2,22) = 0.84, ns) kapa lipalo tsa locomotor (F (2,22) = 1.72, ns), leha tekanyetso e phahameng e ile ea eketsa likhetho tsa khetho libakeng tse 'ne (F ( 2,22) = 3.54, p <0.05 le Dunnett's, p <0.05; Tafole 1).
Tlhatlhobo ea Win-rest / lahleheloa ke phetoho
Li-infusions tsa li-agonists tsa D1 kapa D2 receptor agonists kapa mohanyetsi ho PFC e kahare e hlahisitse litlamorao tse fapaneng ho etseng liqeto. Ho fumana leseli le eketsehileng mabapi le hore na kalafo tsena li amme mekhoa ea khetho le liphetoho tse hlahisitsoeng ke litheolelo, re ile ra etsa tlhahlobo e tlatselletsang ea data ea khetho. Haholo-holo, re ile ra etsa tlhahlobo ea khetho ea khetho ho khetholla hore na liphetoho tsa boits'oaro li bakiloe ke liphetoho tse ka bang teng molemong oa ho khetha lever e kotsi kamora ho fumana moputso o moholo (ts'ebetso ea ho lula hofihlela) kapa liphetoho liphellong tse mpe tsa maikutlo tshebetso) (Bari et al., 2009; Stopper le Floresco, 2011). Likhetho tsa liphoofolo nakong ea mosebetsi li ile tsa hlahlojoa ho latela sephetho sa teko ka ngoe ea khetho ea mahala (moputso kapa moputso) mme ea hlahisoa e le karolelano. Karolo ea liteko tsa win-stay e baliloe ho tloha palong eo rat e khethileng lever e kholo / e kotsi kamora ho khetha khetho e kotsi tekong e fetileng le ho fumana moputso o moholo (win), o arotsoe ke palo e felletseng ea khetho ea mahala liteko tseo ho tsona rat e ileng ea fumana moputso o moholo. Ka lehlakoreng le leng, ts'ebetso ea ho felloa ke matla e ile ea baloa ho tloha makhetlo ao likhoto li fetotseng khetho ho ea ho lever le lenyenyane kamora ho khetha khetho e kotsi tekong e fetileng mme ha ba ka ba putsoa (tahlehelo), ba arotsoe ke palo e felletseng ea liteko tsa khetho ea mahala. ho baka tahlehelo.
Ka lebaka la sebopeho sa mosebetsi, litekong tse 'ne ho ne ho na le maemo a 4-5 moo phoofolo ka' ngoe e sa kang ea khetha lere e kholo / e kotsi (ka hona, e neng e sa khone ho "lula" kapa ho "fetohela" kamora ho hapa kapa tahlehelo) kapa ha a ka a fumana moputso o moholo ho hang nakong ea thibelo e itseng (haholo-holo lithibelo tse peli tsa morao-rao). Ka hona, ho e 'ngoe ea linyeoe tsena, mokhathala ho equation e sebelisitsoeng ho etsa likhakanyo tsena e ka ba zero bonyane ba lithibelo, tse ileng tsa re thibela ho etsa tlhahlobo-leseling ea li-block. Ho hlola sena, tlhahlobo e ile ea etsoa bakeng sa liteko tsohle ho pholletsa le li-block tse 'ne, joalo ka ha re entse pejana (Stopper and Floresco, 2011). Liphetoho ts'ebetsong ea katleho ea win-li sebelisitsoe e le pontšo ea kakaretso ea tšusumetso eo ho fumana moputso o moholo, o kotsi o bileng le ts'usumetso e latelang ea boits'oaro, athe liphetoho lipuisanong tsa tahlehelo ea phetoho li ile tsa fana ka tlhahiso ea maikutlo a fosahetseng nakong eohle ea tlhahlobo seboka.
Ha re fuoa hore e 'ngoe le e' ngoe ea metsoako ena e mene e bakile litlamorao tse ikhethang ketsong ea boits'oaro, re ne re thahasella haholo ho bapisa ka kotloloho litlamorao tsa kompone ka 'ngoe e amanang le kalafo ea letsoai. Bakeng sa tlhahlobo ena, re sebelisitse tlhaiso-leseling e fumanoeng kamora kalafo ka litekanyetso tse sebetsang ka ho fetesisa tsa sethethefatsi se seng le se seng le liente tse tsamaellanang tsa koloi (bakeng sa SKF81297, re sebelisitse data e fumanoeng kamora kalafo ka tekanyetso e tlase ea 0.1 μg) Tlhatlhobo ea liteko tsa win-stay le li-switch-shift li senotse ts'ebelisano e kholo ea litsela tse 'ne tsa mofuta oa teko (win-stay vs lose-shift) × kalafo (saline vs drug) × receptor (D1 vs D2) × mofuta oa lithethefatsi (mohanyetsi vs agonist ) (F (1,44) = 11.92, p <0.05; Setšoantšo sa 4, Letlapa la 2). Joalokaha ho bonoe ka tlhahlobo ea boits'oaro bo akaretsang, tšebelisano-mmoho ea litsela tse 'ne e ne e susumetsoa ke taba ea hore sethethefatsi se seng le se seng se ile sa baka tšusumetso e ikhethang mekhoeng ea win-stay / lose-shift. Mabapi le ts'ebetso ea ho lula u hlotse, tlasa maemo a laoloang, likhoto li bontšitse tloaelo e matla (lipakeng tsa 80 le 90%) ho khetha lever e kotsi kamora ho khetha lever ena tekong e fetileng le ho amohela moputso, joalo ka ha re bone pejana (Stopper le Floresco , 2011). Ka lehlakoreng le leng, liphoofolo li ne li tloaetse ho fetohela ho lever e nyane / e itseng kamora "tahlehelo" kamora ho khetha lever e kholo / e kotsi ho -25-30% ea liteko tsena tlasa maemo a taolo.
Setšoantšo sa 4.
Litlamorao tsa ho fetoloa ha li-PFC DA ka li-win-rest (grey bar) le litloaelo tsa tahlehelo (li-white bar) litloaelo. Bakeng sa ho hlaka le ho bapisa, datha li hlahisoa mona ho latela palo ea phapang pakeng tsa karolelano e fumanoeng litlamorao tsa kalafo ea lithethefatsi (litekanyetso tse ntle li supa keketseho e matla, litekanyetso tse mpe tsa ho fokotseha kamora ho kalafo ea lithethefatsi ho laola infusions). Lintlha tse sa sebetseng tse sebelisitsoeng tlhahlobisong e felletseng eo lintlha tsena li fumanoeng li hlahisoa ho Tafole 2. Methati ea Win-lula e supa karolo ea liteko tseo likhoto li ileng tsa khetha lever e kholo / e kotsi kamora ho amohela moputso o moholo tekong e fetileng. Loss-shift ratios e supa karolo ea liteko tseo likhoto li fetotseng khetho ho ea nyane / letheka le itseng kamora khetho e sa lefelloeng ea lever e kholo / e kotsi. Linaleli li bolela phapang ea bohlokoa ho tloha letsoai le boemong ba 0.05. ns, ha e bohlokoa.
Tafole 2.
Metsoako ea Win-lula / lahleheloa ke phetoho bakeng sa likhoto tse etsang mosebetsi oa ho theola litheko ha ho latela moralo oa moriana le lethal dose le phahameng ka ho fetisisa kapa le sebetsang ka ho fetisisa la D1 le D2 antagonist kapa agonists
Tlhatlhobo e kholo ea litlamorao tsa tšebelisano-mmoho ea litsela tse 'ne e senotse hore mohanyetsi oa D1 SCH23390 ha a ame ts'ebetso ea ho lula ha win empa o ekelitse haholo litloaelo tsa tahlehelo (Dunnett's, p <0.05), a fana ka maikutlo a hore phokotso ea khetho e kotsi e bakiloeng ke liphekolo tsena Karolo e 'ngoe e ka bakoa ke keketseho ea kutlo ho maikutlo a fosahetseng (ke hore, tlohelo ea moputso). Ka lehlakoreng le leng, thibelo ea D2 e nang le eticlopride (1 μg) e ekelitse haholo menyetla ea ho khetha khetho e kotsi ka mor'a "win" (p <0.05), ha e ntse e baka phokotso e sa reng letho mekhoeng ea tahlehelo. Kahoo, keketseho ea khetho e kotsi e hlohlellelitsoeng ke thibelo ea D2 e bonahala e bakoa haholo-holo ke tšusumetso e ntlafalitsoeng ea ho fumana moputso o moholo ho khetho e latelang.
D1 agonist SKF81297 (0.1 μg) e ekelitse ts'ebetso ea win-stay haholo le saline (p <0.05), empa hape e bile le litlamorao tse fapaneng le tsa SCH23390, e fokotsa tloaelo ea ho fetoha kamora tahlehelo e tsoang ho lever e kholo / e kotsi (p <0.05) . Ka lehlakoreng le leng, quinpirole (10 μg) e bile le litlamorao tse fapaneng tsa agonist ea D1 litloaelong tsa ho lula, ka ho fokotsa haholo monyetla oa ho khetha lever e kholo / e kotsi ka mor'a "win" (p <0.05), e fana ka maikutlo a hore ho tla ba bonolo ho amohela ea meputso e meholo, empa e sa tsitsang. Kalafo ena e ne e se na tšusumetso e kholo litekanyetsong tsa ho lula ha batho. Liphuputso tsena li bonts'a hore ho feto-fetoha ha molumo oa li-receptor tsa D1 vs D2 ho baka liphetoho tse fapaneng ts'ebetsong e khethiloeng e bonahalang e khetholloa ke liphetoho tse fapaneng litlamong tsa ho fumana moputso o moholo kapa kutloisiso e mpe ea maikutlo.
Moputso khethollo ea boholo
Li-blockade tsa li-receptors tsa D1 kapa tse tsosang takatso ea li-receptors tsa D2 li fokolitse khetho ea moputso o moholo, o sa tsitsang nakong ea lithibelo tse itseng tsa liteko tsa mosebetsi oa ho theola. Ho lekola hore na litlamorao tsena li bakiloe ke pherekano e akaretsang ea khethollo pakeng tsa meputso e mengata, re ile ra etsa teko e 'ngoe, moo lihlopha tse peli tse arohaneng tsa likhoto li koetliselitsoeng mosebetsi o bobebe. Likhoto li khethile lipakeng tsa likhama tse peli tse tsamaisang pellets e le 'ngoe kapa tse' ne, ka bobeli ba monyetla oa 100%. Liroto tse leshome le metso e mehlano li ile tsa koetlisetsoa 11 d mosebetsing ona pele li fumana li-microinfusions tse loantšang tekanyetso e phahameng ea SCH23390 (1 μg) kapa quinpirole (10 Xg) le saline. Lintlha tsa phoofolo e le 'ngoe li tlositsoe ka lebaka la ho beoa ka nepo, li siea n ea ho qetela ea 6 sehlopheng sa SCH23390 le 8 sehlopheng sa quinpirole.
D1 blockade
Kamora ho ts'oaetsoa ke letsoai, likhoto li bonts'itse leeme le leholo ho moputso o moholo, ho khetha khetho ena ho liteko tse ka bang 100% (Setšoantšo sa 5A). Kamora ho ts'oaetsoa ke SCH23390 (1 μg), ho ne ho se phetoho e khethiloeng mabapi le khetho ea pellet (F (1,5) = 1.72, ns). Ho fapana le khetho, re bone keketseho e nyane ea likarolo tsa karabelo kamora ho koaloa ha D1 (saline = 0.81 ± 0.1 s, SCH23390 = 0.98 ± 0.1 s; F (1,5) = 7.18, p <0.05). Ketsahalo ea locomotor (F (1,5) = 4.86, ns) le ho tloheloa ha liteko (F (1,5) = 1.0, ns) ha lia angoa ke SCH23390. Kahoo, leha infusions ea lethal dose ea SCH23390 e fokolitse khetho ea moputso o moholo nakong ea mosebetsi oa ho theola, phello ena ha e bonahale e ka bakoa ke phokotso e akaretsang ea boleng bo ikhethang ba meputso e meholo.
Setšoantšo sa 5.
Litlamorao tsa ho feto-fetoha ha methapo ea DA ho MDC ea moruo mabapi le khethollo ea boholo ba meputso. Liroto li ile tsa koetlisetsoa ho khetha lipakeng tsa likhoto tse peli tse fanang ka moputso oa tse 'ne kapa e le' ngoe hang kamora mochine o le mong o nang le monyetla oa 100%. A, D1 blockade (SCH23390, 1 μg) ha ea ka ea senya haholo khetho ea moputso o moholo oa li-pellet tse nne nakong ea liteko tsa khetho ea mahala tse amanang le kalafo ea saline. B, D2 receptor stimulation (quinpirole, 10 μg) le eona ha e a ka ea fetola khetho ea moputso o moholo.
D2 receptor e susumetsang
Tlaleho e tšoanang ea khetho e ile ea bonoa bakeng sa likhoto tse fumanang lethal dose e phahameng (10 μg) ea quinpirole ho PFC e bohareng. Hape, likhoto li khethile khetho ea maqhubu a mane ho hoo e ka bang liteko tsohle tsa khetho ea mahala kamora infusions ea letsoai. Khetho ena ha ea ka ea fetoloa ke ho hlohlelletsa li-receptor tsa D2 (F (1,6) = 0.53, ns; Setšoantšo sa 5B). Quinpirole le eona e ne e se na tšusumetso e kholo ho latency, locomotion, kapa omissions (litekanyetso tsohle tsa F <1.76, ns). Hlokomela hore kalafo tse ts'oanang li fokolitse khetho ea moputso o moholo mosebetsing oa monyetla oa ho theolelo nakong ea pele, 100% ea monyetla oa ho ba teng (Setšoantšo sa 3B). Tlhaloso e ka bang teng ea phapang ena ke hore, ho fapana le likhoto tse koetliselitsoeng khethollo ea boholo ba moputso, ba koetlisitsoeng mosebetsing oa litheolelo ba ithutile hore ts'ebeliso e lekanyelitsoeng ea khetho e kholo / e kotsi e ea fokotseha nakong ea thuto. Kahoo, boemeli ba bona ba boleng bo lekanyelitsoeng ba khetho e kholo ea moputso bo ka lebelloa hore bo be thata ho feta ba likhoto tse koetliselitsoeng mosebetsi o bobebe, ka hona, li ka hlaseloa habonolo. Ka kakaretso, liphetho tsa teko ena li bonts'a hore leha thibelo ea li-receptor tsa D1 le tšusumetso ea li-receptor tsa D2 li fetola likhetho haholo lipakeng tsa meputso e menyenyane, e itseng le e kholo, monyetla ona, litlamorao tsena ha li bonahale li bakiloe ke mathata a mantlha molemong oa khethollo lipakeng tsa meputso e meholo le e menyenyane.
Puisano
Mona re tlaleha hore li-D1 le li-receptor tsa D2 ho PFC ea moruo li na le tšusumetso e matla likhethong lipakeng tsa moputso oa bapisoa le meputso e itseng. Ntle le moo, ho fokotsa kapa ho eketsa tšebetso ea e 'ngoe le e' ngoe ea li-receptor tsena ho hlahisitse mefuta e fapaneng, 'me ka linako tse ling ho fapana, liphetoho boikhethong, ho fana ka maikutlo a hore e mong le e mong o fana ka taolo e fapaneng, empa e le tlatsetso ea ho feto-fetoha ha maemo mabapi le lits'ebetso tsa ho etsa liqeto.
Litlamorao tsa D1 / D2 receptor blockade
Ho tsebo ea rona, ena ke pontso ea pele eo blockade ea D1 kapa D2 receptor ho medial PFC e etsang hore ho be le litlamorao tse khahlanong le boitšoaro. Liphuputso tse fetileng tsa mofuta ona li senotse hore na D1, empa eseng D2, antagonism e sitisa mesebetsi e joalo ka tlhokomeliso kapa mohopolo oa ho sebetsa (Williams le Goldman-Rakic, 1995; Seamans et al., 1998; Granon et al., 2000) kapa hore ka bobeli li-receptors li sebetsa ka tšebelisano-'muso ho tsamaisa boitšoaro bo fetotseng kapa ba leeme hole le batho ba tsubang ba nang le maemo (Ragozzino, 2002; Floresco le Magyar, 2006). Liphumano tsa rona tse hlahisoang ke SCH23390 le eticlopride li hlahisitse litlamorao tse fapaneng le khetho e fana ka maikutlo a hore ho nka liqeto tse tloaelehileng ho its'etleha hodima mohato o thata oa ts'ebetso ea pele ea lobe D1 le D2 receptor, le hore ho fetoloa hoa tekano ho etsa hore ho be le liphetoho tse ikhethileng ha ho khethoa meputso e itseng / e sa tsitsang.
PFC D1 blockade e fokotse khethollo bakeng sa khetho e kholo / e kotsi ka mokhoa o itšetlehileng ka litekanyetso, Haholoholoholo nakong ea li-block tse tharo tsa ho qetela. SCH23390 e ekelitse litheko tsa probabilistic, tse tšoanang le litlamorao tsa komporo ena ha e tsamaisoa ka mokhoa o hlophisehileng (St. Onge and Floresco, 2009). Ho khahlisang, ho fokotsa phetisetso ea DA lithutong tsa batho ka ho fokotsoa ha tyrosine ho boetse ho lebisa ho liqeto le ho etsa liqeto tsa boleng bo tlase ho Cambridge Gurb Task (McLean et al., 2004). Liphetho tsa rona li fana ka maikutlo a hore litlamorao tsena li ka kopanngoa ka karolo ka ho kengoa tšebetsong ha D1 pele. Tlhatlhobo ea khetho ka boikhethelo e boetse e senoletse hore khetho ena e fokotsehileng bakeng sa khetho e kotsi e ne e hokahane le tloaelo e atileng ea ho khetha khetho e nyane / e latelang kamora khetho e kotsi e sa lefelloeng, e fana ka maikutlo a hore litlamorao tsa ho etsa liqeto e kanna ea ba sephetho sa keketseho. tlhokomeliso ea maikutlo a fosahetseng. Ka vein e ts'oanang, blockade ea li-receptor tsa D1 ho prelimbic kapa anterior cingulate e fokotsa khetho ea meputso e meholo ha e lieha (Loos et al., 2010) kapa e amanang le litšenyehelo tse kholo tsa boiteko (Schweimer and Hauber, 2006). Ka kopanelo, liphumano tsena li bonts'a hore ho saena ha PFC D1 ho fana ka tšusumetso e kholo litlhahlobisong tsa theko / melemo, ho nolofalletsa bokhoni ba ho hlola litšenyehelo tse ka amanang le meputso e meholo molemong oa ho holisa phaello e telele.
Ho fapana le hoo, PFC D2 receptor blockade e ile ea eketsa khetho bakeng sa khetho e kholo / e kotsi, ea liehisa phetoho ho khetho ea khetho ha menyetla ea meputso e fokotsehile nakong ea thuto. Haholo, phello ena e tšoana le e susumetsoang ke ts'ebetso ea PFC tlasa maemo a tšoanang a mesebetsi (St. Onge and Floresco, 2010). Leha ho le joalo, ha re lumele hore hona ho bonts'a keketseho e akaretsang ea boits'oaro bo “kotsi” ka ho ngoe. Ho fapana le moo, lipatlisiso tsa rona tsa pejana li re lebisitse ho etsa qeto ea hore PFC ea moruo e bapala karolo ea bohlokoa ho lekola liphetoho menyetla ea meputso ho fetola boitšoaro ka mokhoa o tšoanang. Liphetho tsa hona joale li atoloha ho sena, li senola hore li-receptors tsa D2 li kenya letsoho ho bohlokoa ho taolo ea PFC ea karolo ena ea liqeto. Keketseho ena e totobetseng ea khetho e kotsi e ile ea tsamaisoa ka mokhoa o hlakileng haholoanyane ke tšekamelo e eketsehileng ea ho khetha khetho e kotsi ka mor'a ho fumana moputso o moholo tekong e fetileng. Kahoo, ho fapana le ho kopanya leseli mabapi le menyetla ea ho fumana moputso o moholo ho feta liteko tse ngata, D2 blockade e ile ea etsa hore ho fumana moputso o moholo ho hlahise phello e kholo le e potlakileng haholoanyane ntlheng ea khetho e latelang. Sena se tsamaisana le phuputso ea morao-rao ho batho, eo ho eona mohanyetsi oa D2 a ileng a eketsa khetho ea likhetho tse amanang le menyetla e mengata ea moputso le liphetoho tse lumellanang tšebetsong ea mosebetsi oa PFC (Jocham et al., 2011). Ka kopanelo, liphumano tsena li bonts'a hore li-receptors tsa PFC D1 le D2 li theha likarolo tse ikhethileng, empa li tlatselletsa ho etsa liqeto. Ts'ebetso ea li-receptor ea D1 e khothalletsa khetho ea meputso e meholo, empa e sa tsejoe kapa e theko e phahameng, athe li-receptors tsa D2 li fokotsa tšusumetso eo kapele, meputso e makatsang e fanang ka khetho e kholo, e nolofalletsang bokhoni ba ho fetola boitšoaro ka nako e telele ha monyetla oa ho fumana meputso ona liphetoho.
Litlamorao tsa D1 / D2 receptor
Intra-PFC infusions ea D1 receptor agonist SKF81297, ka har'a methapo ea lipalo e bonts'itsoeng e fana ka litlamorao tse fapaneng mefuteng e meng ea kelello (tlhokomeliso, mohopolo oa ho sebetsa), ha ea ka ea fetola khetho e kotsi haholo, leha mekhoa ena ea kalafo e eketsehile hanyane bakeng sa e kholo / lever e nang le kotsi, haholo ka haholo le lethalinyana le tlase. Tlhaloso ea phello ena e se nang thuso e lokela ho atameloa ka hloko, hobane litla-morao tsa / non-monotonic lethathamo la karabelo e sa supe hore SKF81297 e kanna ea ba le lethathamo la lethalinyana le sebetsang ho feta le ka bang teng bakeng sa mesebetsi e meng ea kelello. Ho feta moo, lethalamo la 0.1 μg le ile la fetola mekhoa ea khetho, la eketsa ts'ebetso ea win-lula le ho fokotsa litloaelo tsa tahlehelo, moo likhoto li neng li khona ho khetha lever e kholo / e kotsi kamora ho fumana moputso le moputso o mong. Leha ho le joalo, taba ea hore tekanyetso e ntseng e eketseha ea SKF81297 ha e ea ka ea fetoha haholo khetho e bontša hore ho susumetsoa haholo ha li-receptors tsa PFC D1 ha ho kena-kenane le ho etsa liqeto mabapi le likotsi le meputso. Ho fapana le hoo, kalafo e ts'oanang e fokotsa khetho ea meputso e meholo, e liehang (Loos et al., 2010), e fana ka ts'ehetso e eketsehileng ea hore mefuta e fapaneng ea ho etsa liqeto tsa phaello / phaello e ka arohanngoa le meriana.
D2 agonist quinpirole e bakile "ho sitisoa" ha 'nete ho etseng liqeto, e pepeta lekhapetla le litheko,' me likhoto li sa bontše phokotso e hlakileng mabapi le liphetoho lipapatsong tsa meputso. Khetho ea likhetho tsa li-pellet tse 'ne e fokotsehile ka har'a 100% block (ha e ne e le molemo haholo), empa e ile ea eketseha ka 12.5% block (ha e na le molemo o moholo). Kamora ho hlohlelletsoa ha D2, karolo e akaretsang ea likhetho tse kholo / tse kotsi ha e a fetoha mabapi le letsoai (∼73%), empa liphoofolo li ne li sa tsotelle letho ka liphetoho tse ka bang teng. Kahoo, ts'ebetso ea li-receptor e feteletseng ea D2 e kena-kenane haholo le bokhoni ba ho fetola khetho, ho bonahala e etsa hore likhoto li sebelise leano le bonolo la ho fetoloa lits'ebetsong ha li ntse li boloka leeme ho lever e kholo / e kotsi. Ho fumana hona, hammoho le litlamorao tsa eticlopride, e fana ka maikutlo a hore maemo a amanang le D2 (ho fapana le D1) molumo oa li-receptor ho MDC ea maqhubu o na le tšusumetso e matla ntlheng ena ea ho etsa liqeto, mme ho eketsa kapa ho fokotsa ketsahalo ena ho ka sitisa tšebetso..
Mokhoa o seng monate oa khetho o hlahisoang ke quinpirole o tšoana le o ts'oaroang ka ho fokotsa tšusumetso ea lijo ka phepelo ea nako e telele ea mahala (St. Onge le Floresco, 2009). Liphumano tsena tse tlatsetsang li etsa hore e leke ho nahana hore e kanna ea ba liketsahalo tse amanang. Kannete, ho entsoe liphetoho lipakeng tsa motlakase oa PFC DA hore li bonts'e moputso oa lijo ka kakaretso kapa lets'usumetso la khothatso (Ahn le Phillips, 1999; Winstanley et al., 2006). Kahoo, liphetoho lipapatsong tsa moputso tse fumanoeng ha nako e ntse e feta li ka tšoaetsoa ho PFC ka ho feto-fetoha ha maemo ho lumellanang ha maemo a mesocortical DA hoo ka liketso tse fumanehang ho D2 receptors, li ka sebelisoang ho fumana liphetoho molemong oa moputso o fumaneng nako e telele le ho tsamaisa liphetoho ho khetho ea leeme. Ho latela hore meroallo ea D2 receptors e ka senya pontšo ena e matla, eo qetellong e ka hlahisang mekhoa e mengata ea khetho.
Menehelo e ke keng ea hlakoloa ea li-receptors tsa PFC D1 le D2 ho etsa liqeto tse thehiloeng kotsing
Potso e sala hore na ke hobaneng blockade ea D1 kapa D2 receptors e lokela ho hlahisa litholoana tse hanyetsanang le khetho e kotsi, ha feela DA e le semmuso e kenya li-receptor ka bobeli. Khopolo ea mehleng ena ea hore li-receptors tsena li ama ts'ebetso ea marang-rang ea neano ea PFC ka tsela e fapaneng e ka fana ka leseli mabapi le bothata bona (Durstewitz et al., 2000; Seamans le Yang, 2004). Li-receptors tsa D1 li reriloe hore li fokotse tšusumetso ea lisebelisoa tse fokolang, ho tiisa ts'ebetso ea marang-rang e le hore tlhahiso e le 'ngoe e laole tlhahiso ea PFC. Ka lehlakoreng le leng, ts'ebetso ea D2 e bonts'a litšusumetso tse thibelang, ho lumella li-enCC tsa mofuta oaCCC ho sebetsa liphatlalatso tse ngata / tse tsosang maikutlo, li beha marang-rang a litaba maemong a sebetsang a mangata a ka lumellang liphetoho ho boemeli..
Nakong ea likarolo tse fapaneng tsa mosebetsi oa ho fokotsa litheko tse sebelisitsoeng mona, liphoofolo ka nako tse ling li tlameha ho boloka (ka har'a leseli) kapa ho fetola (ka li-block) tlhahiso ea boleng bo lekanyelitsoeng ba khetho e kholo / e kotsi. Ka hona, litlamorao tse hanyetsanang tsa ho qhekella tsa D1 / D2 tse hlalositsoeng mona li ka bonts'a phano ea phapang ea li-receptors tsena ka mekhahlelo e fapaneng ea mosebetsi. Ts'ebetso ea D1 e ka tsitsisa moemeli oa boleng ba nako e telele ba khetho e kotsi ka har'a mofuta o itseng, ho boloka khetho e le joalo leha khetho e kotsi e ka lebisa ho setseng (ho boloka "leihlo ho moputso"). Ho thibela li-receptor tsena ho ka etsa hore liphoofolo li amehe haholo ka moputso (ke hore, ho eketsa mekhoa ea ho lahleheloa ke phetoho) le ho fokotsa khetho e kotsi. Ka lehlakoreng le leng, ha khetho e kholo / e kotsi e hlahisa meputso e fokolang ho li-block, li-receptors tsa D2 (mohlomong ho sechaba se fapaneng sa neuronal) li ka tsamaisa liphetoho tse hlahisitsoeng molemong oa tlhahiso. Kahoo, ho fokotsa ts'ebetso ea bona ho ka sitisa ntlafatso ea lipontšo tsena le liphetoho tse tsamaellanang le khetho e ntle. Moetso ona o kanna oa nka karolo bakeng sa litlamorao tsa ho eketseha ha mosebetsi oa D1 le D2, tse ka lebelloang ho lebisa ho khethoeng ha khetho e kholo ea khetho e kholo / e kotsi kapa ho etsa hore ho be le "hyperflexible" state. Kahoo, liphumano tsa rona li fana ka maikutlo a hore molumo oa PFC DA o etsa tlatsetso e boima le e rarahaneng ea ho ahlola likotsi tsa meputso / moputso. Ka ho etsa tekatekano e ntle pakeng tsa ts'ebetso ea li-receptor ea D1 / D2, mesocortical DA e ka thusa ho ntlafatsa liqeto tsa theko / melemo lipakeng tsa likhetho tsa boholo bo sa ts'oaneng le ho se tsitsinyehe, ho khothaletsa tšebeliso ea maemo a hona joale a matle kapa tlhahlobo ea ba nang le phaello e ngata ha maemo a fetoha.
Mongolo o botlaaseng ba leqephe
Mosebetsi ona o tšehelitsoe ke chelete e tsoang ho Canadian Institutes of Health Research (MOP 89861) ho SBFSBF ke Michael Smith Motheo oa Boithuto ba Bophelo bo Botle Senior Scholar mme JRSO ke moamoheli oa lithuto ho tsoa ho Lekhotla la Saense la Tlhaho le Boenjineri ba Canada le Michael Smith Motheo oa Patlisiso ea Bophelo.
Litaba li lokela ho lebisoa ho Dr. Stan B. Floresco, Setsi sa Psychology le Brain Research Center, Univesithi ea British Columbia, 2136 West Mall, Vancouver, BC V6T 1Z4, [imeile e sirelelitsoe]
Copyright © 2011 bangoli ba 0270-6474 / 11 / 318625-09 $ 15.00 / 0
References
1. ↵
1. Ahn S,
2. Phillips AG
(1999) Li-dopaminergic lihokelo tsa satiety tse ikhethileng tsa sensory ho "cortex" ea methapo ea methapo le methapo ea mokokotlo ea rat. J Neurosci 19: RC29, (1-6).
Sephiri / Text Full FREE
2. ↵
1. Bardgett ME,
2. Depenbrock M,
3. Downs N,
4. Lintlha M,
5. Green L
(2009) Dopamine e fetolela liqeto tse thehiloeng boitekong lihlopheng tsa likhoto. Behav Neurosci 123: 242-251.
CrossRefMedline
3. ↵
1. Bari A,
2. Dikolo-ntsu,
3. Mar AC,
4. Robinson ES,
5. Robbins TW
(2009) Litlamorao tse sa lumellaneng tsa Noradrenaline, dopamine, le serotonin uptake blockade on performance task in rats. Psychopharmacology 205: 273-283.
CrossRefMedline
4. ↵
1. Mok'hadinale RN,
2. Howes NJ
(2005) Liphello tsa ho ruruha ha sekhahla li bokellana molemong oa khetho pakeng tsa meputso e nyane le meputso e meholo e sa tsitsang ho likhoto. BMC Neurosci 6: 37.
CrossRefMedline
5. ↵
1. Mok'hadinale RN,
2. Robbins TW,
3. Zheng BJ
(2000) Litlamorao tsa d-amphetamine, chlordiazepoxide, alpha-flupenthixol le boitšoaro bo hlephileng mabapi le khetho ea ho tiisoa le ho sa ngolisoe ka tieo ha litlamo. Psychopharmacology 152: 362-375.
CrossRefMedline
6. ↵
1. Chudasama Y,
2. Robbins TW
(2004) Ho feto-fetoha ha maikutlo a dopaminergic bakeng sa tlhokomelo ea pono le mohopolo oa ho sebetsa sebakeng sa pele sa "centex" sa pele. Neuropsychopharmacology 29: 1628-1636.
CrossRefMedline
7. ↵
1. Cousins MS,
2. Wei W,
3. Salamone JD
(1994) Ts'oaetso ea pharmacological ea ts'ebetso ho mokhoa o ts'oanang oa khatello ea lever o hatellang / oa ho fepa: litlamorao tsa dopamine antagonist, cholinomimetic, lithethefatsi tse susumetsang le tse susumetsang. Psychopharmacology 116: 529-537.
CrossRefMedline
8. ↵
1. Denk F,
2. Walton ME,
3. Jennings KA,
4. Sharp T,
5. Rushworth MF,
6. Bannerman DM
(2005) Ho kenella ka mokhoa o fapaneng oa tsamaiso ea serotonin le dopamine liqetong tse amanang le melemo mabapi le ho lieha kapa boiteko. Psychopharmacology 179: 587-596.
CrossRefMedline
9. ↵
1. Durstewitz D,
2. Seamans JK,
3. Sejnowski TJ
(2000) Meetso e sa sebetseng ea memori e sebetsang. Nat Neurosci 3 (Suppl): 1184-1191.
CrossRefMedline
10. ↵
1. Floresco SB,
2. Magyar O
(2006) Mesocortical dopamine modulation ea mesebetsi e phahameng: ntle le memori e sebetsang. Psychopharmacology 188: 567-585.
CrossRefMedline
11. ↵
1. Floresco SB,
2. Whelan JM
(2009) Ho sesa ka mefuta e fapaneng ea ho etsa liqeto ka theko / melemo e hlahisoang ke ho pepesetsoa hoa amphetamine. Psychopharmacology 205: 189-201.
CrossRefMedline
12. ↵
1. Floresco SB,
2. Magyar O,
3. Kahds-Sharifi S,
4. Vexelman C,
5. Tse MT
(2006) Li-receptor tse ngata tsa dopamine tse ngata tse fumanehang ka har'a cortex ea medial prefrontal ea rat e laola ho fetoha ha linako. Neuropsychopharmacology 31: 297-309.
CrossRefMedline
13. ↵
1. Floresco SB,
2. Tse MT,
3. Maholimo-Sharifi S
(2008a) Dopaminergic le melaoana ea glutamatergic ea ho etsa boiteko le ho nka liqeto tse thehiloeng kapele. Neuropsychopharmacology 33: 1966-1979.
CrossRefMedline
14. ↵
1. Floresco SB,
2. St Onge JR,
3. Kahds-Sharifi S,
4. Winstanley CA
(2008b) Li-circuits tsa li-Cortico-limbic-striatal tse fanang ka mefuta e fapaneng ea ho etsa liqeto ka theko. Cogn Afate Behav Neurosci 8: 375-389.
CrossRefMedline
15. ↵
1. Kahds-Sharifi S,
2. St Onge JR,
3. Floresco SB
(2009) Tlatsetso ea mantlha ke basyati ea basolateral mefuta e fapaneng ea ho etsa liqeto. J Neurosci 29: 5251-5259.
Sephiri / Text Full FREE
16. ↵
1. Granon S,
2. Passetti F,
3. Sandra KL,
4. Dalley JW,
5. Lisa BJ,
6. Robbins TW
(2000) Ts'ebetso e ntlafalitsoeng le e senyehileng ea ts'ebetso ka mor'a ho kenngoa ha li-receptor tsa D1 dopaminergic receptor ho rat prefrontal cortex. J Neurosci 20: 1208-1215.
Sephiri / Text Full FREE
17. ↵
1. Haluk DM,
2. Floresco SB
(2009) Ventral striatal dopamine modulation ea mefuta e fapaneng ea boitšoaro bo feto-fetohang. Neuropsychopharmacology 34: 2041-2052.
CrossRefMedline
18. ↵
1. Hutton SB,
2. Murphy FC,
3. Joyce EM,
4. Rogers RD,
5. Cuthbert I,
6. Barnes TR,
7. McKenna PJ,
8. Sahakian BJ,
9. Robbins TW
(2002) Qeto e etsang likoloto ho bakuli ba nang le karolo ea pele le lefu la kelello le sa foleng. Schizophr Res 55: 249-257.
CrossRefMedline
19. ↵
1. Jocham G,
2. Klein TA,
3. Ullsperger M
(2011) Lipontšo tsa ho matlafatsa tsa dopamine-mediated tsa ho matlafatsa lithutong tsa striatum le li-ventromedial prefrontal cortex tlasa likhetho tse thehiloeng holima boleng. J Neurosci 31: 1606-1613.
Sephiri / Text Full FREE
20. ↵
1. Loos M,
2. Pattij T,
3. Janssen MC,
4. Counotte DS,
5. Schoffelmeer AN,
6. Smit AB,
7. Spijker S,
8. van Gaalen MM
(2010) Dopamine receptor D1 / D5 gene polelo ea medial prefrontal cortex e bolela esale pele khetho e sa qobelloang ho litoeba. Cereb Cortex 20: 1064-1070.
Sephiri / Text Full FREE
21. ↵
1. McLean A,
2. Rubinsztein JS,
3. Robbins TW,
4. Sahakian BJ
(2004) Litlamorao tsa ho theoha ha tyrosine ho baithaopi ba phetseng hantle: litlamorao tsa ho tepella maikutlo ho sa feleng. Psychopharmacology 171: 286-297.
CrossRefMedline
22. ↵
1. Pagonabarraga J,
2. García-Sánchez C,
3. Llebaria G,
4. Pascual-Sedano B,
5. Gironell A,
6. Kulisevsky J
(2007) Phuputso e laoloang ea ho nka liqeto le ts'oaetso ea ts'oaetso ho lefu la Parkinson. Mov Disord 22: 1430-1435.
CrossRefMedline
23. ↵
1. Paxinos G,
2. Watson C
(1998) Boko ba likhoto ho litlhophiso tsa stereotaxic (Boikoetliso, San Diego), Ed 4.
24. ↵
1. Ragozzino ME
(2002) Litlamorao tsa dopamine D (1) li-receptor blockade libakeng tsa prelimbic-infralimbic mabapi le boitšoaro bo fetohang. Ithute Mem 9: 18-28.
Sephiri / Text Full FREE
25. ↵
1. Rogers RD,
2. Lisa BJ,
3. Baldacchino A,
4. Fekete AJ,
5. Swainson R,
6. Wynne K,
7. Baker NB,
8. Hunter J,
9. Carthy T,
10. Booker E,
11. London M,
12. Deakin JF,
13. Sahakian BJ,
14. Robbins TW
(1999) Lits'oaetso tse ka sitoang ho etsa liqeto mabapi le ho hlekefetsa ba hlekefetsang ba amphetamine, bahlaseli ba opiate, bakuli ba nang le tšenyo e kholo ea li-cortex tsa pele, le tryptophan-e felisang baithaopi ba tloaelehileng: bopaki ba mekhoa ea monoaminergic. Neuropsychopharmacology 20: 322-339.
CrossRefMedline
26. ↵
1. Schweimer J,
2. Hauber W
(2006) Dopamine D1 receptors ka anterior cingrate cortex e laola liqeto tse thehiloeng hodima boiteko. Ithute Mem 13: 777-782.
Sephiri / Text Full FREE
27. ↵
1. Schweimer J,
2. Saft S,
3. Hauber W
(2005) Ho kenella ha catecholamine neurotransmission ho cterote ea ka ntle ea rat ho etsa liqeto tse amanang le boiteko. Behav Neurosci 119: 1687-1692.
CrossRefMedline
28. ↵
1. Seamans JK,
2. Yang CR
(2004) Lintlha tse ka sehloohong le mekhoa ea ho feto-fetoha ha dopamine ka cortex ea pele. Prog Neurobiol 74: 1-58.
CrossRefMedline
29. ↵
1. Seamans JK,
2. Floresco SB,
3. Phillips AG
(1998) D1 receptor modulation ea li-circuits tsa hippocampal-pele tsa nako e kopanyang memori ea sebaka le mesebetsi e phahameng ho rat. J Neurosci 18: 1613-1621.
Sephiri / Text Full FREE
30. ↵
1. St Onge JR,
2. Floresco SB
(2009) Ho feto-fetoha ha maikutlo ka Dopaminergic ea ho etsa liqeto tse behiloeng kotsing. Neuropsychopharmacology 34: 681-697.
CrossRefMedline
31. ↵
1. St Onge JR,
2. Khoa YC,
3. Floresco SB
(2010) Liphetoho tse fapaneng tsa dopaminergic manipulla mabapi le khetho e kotsi. Psychopharmacology 211: 209-221.
CrossRefMedline
32. ↵
1. St Onge JR,
2. Floresco SB
(2010) Tlatsetso ea pele ea cortical ea ho etsa liqeto tse behiloeng kotsing. Cereb Cortex 20: 1816-1828.
Sephiri / Text Full FREE
33. ↵
1. Stopper CM,
2. Floresco SB
(2011) Menehelo ea li-bokellase ea li-nucleus le likarolo tsa eona ho likarolo tse fapaneng tsa ho etsa liqeto tse behiloeng kotsing. Cogn Afate Behav Neurosci 11: 97-112.
CrossRefMedline
34. ↵
1. van Gaalen MM,
2. van Koten R,
3. Schoffelmeer AN,
4. Vanderschuren LJ
(2006) Ho kenella ka matla ho dopaminergic neurotransmission ho etsa liqeto tse sa potlakiseng. Biol Psychiatry 60: 66-73.
CrossRefMedline
35. ↵
1. Williams GV,
2. Goldman-Rakic PS
(1995) Modulation ea masimo a memori ka dopamine D1 receptors ka cortex ea pele. Nature 376: 572-575.
CrossRefMedline
36. ↵
1. Winstanley CA,
2. Theobald DE,
3. Dalley JW,
4. Robbins TW
(2005) Litšebelisano lipakeng tsa serotonin le dopamine taolong ea khetho e sa qobelloeng ho litoeba: litlamorao tsa kalafo bakeng sa mathata a taolo a sa laoleheng. Neuropsychopharmacology 30: 669-682.
Medline
37. ↵
1. Winstanley CA,
2. Theobald DE,
3. Dalley JW,
4. Mok'hadinale RN,
5. Robbins TW
(2006) Ho ikhetholla habeli pakeng tsa serotonergic le dopaminergic modular ea medial predomal and orbitofrontal cortex ea khetho e sa qoso. Cereb Cortex 16: 106-114.
Sephiri / Text Full FREE
;