Dopamine le moputso: anthonia hypothesis lilemo tse 30 holimo. (2008)

THUTO E TLAHANG

PMCID: PMC3155128
NIHMSID: NIHMS314106
Roy A. Bohlale*
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Moetso oa khatiso oa ho qetela oa mohatisi o fumaneha ho Neurotox Res
Sheba lihlooho tse ling ho PMC hore Qotsa sehlooho se hatisitsoeng.
Eya ho:

inahaneloang

Anhedonia hypothesis - hore boko dopamine e bapala karolo ea bohlokoa thabong e tlisoang ke moputso o motle - e ne e reretsoe ho hohela tlhokomelo ea lingaka tsa mafu a kelello ho bopaki bo ntseng bo hola ba hore dopamine e bapala karolo ea bohlokoa ho matlafatsong ea sepheo le ts'usumetso e khothalletsoang e amanang le lijo le metsi. , moputso oa ho susumetsa ha kelello, le moputso oa psychomotor le moputso oa opiate. Hypothesis e hlokomelisitse taba e makatsang ea hore li-neuroleptics, lithethefatsi tse sebelisetsoang ho phekola boemo bo kenyang anhedonia (schizophrenia), li kenyelletsa liphoofolong tsa laboratori ts'usumetso e ntle eo ka tloaelo re e amahanyang le thabo. Boithuto ba maikutlo bo ile ba ts'oara thahasello e khutšoanyane feela ho litsebi tsa mafu a kelello, ea ileng a supa hore lithuto tsa liphoofolo li bontšitse e thata liketso tsa li-neuroleptics athe kalafo ea lefu la kelello le bonahala e hlaha ho tloha ho li-neuroadaptations ho e sa foleng tsamaiso ea methapo ea kutlo, le hore ke matšoao a botle a schizophrenia ao li-neuroleptics li a fokotsang, ho fapana le matšoao a fosahetseng a kenyeletsang anhedonia. Mohlomong ka mabaka ana, ts'oaetso e bile le tšusumetso e nyane haholo lithutong tsa mafu a kelello. Leha e na le boleng bo lekanyelitsoeng ba ho utloisisa kutloisiso ea schizophrenia, leha ho le joalo, hypothesis ea anhedonia e bile le tšusumetso e kholo lithutong tsa likokoana-hloko tsa ho matlafatsa, ho susumetsa le ho lemalla. Dopamine ea Brain e bapala karolo ea bohlokoa haholo ho matlafatseng mekhoa ea karabelo, likhetho tsa boemo, le polasetiki ea synaptic mefuteng ea ho ithuta le ho hopola. Khopolo ea hore dopamine e bapala karolo e kholo ho matlafatsong ke ea bohlokoa mohopolong oa maikutlo o khothalletsang bokhoba, lithutong tse ngata tsa tumello ea ho lemalla, le likhopolong tsa hona joale tsa boitlamo le maemo a boletsoeng esale pele. Ha e utloisisoa hantle, e bohlokoa hape likhopolong tsa morao-rao tsa tšusumetso ea khothalletso.

Keywords: Dopamine, Moputso, Matlafatso, Khothatso, Anhedondia
Eya ho:

SELELEKELA

Anhedonia hypothesis of koketso ea neuroleptic (Bohlale, 1982) e ne e le, ho tloha qalong ea eona (Ke bohlale et al a., 1978), corollary ea hypotheses tse pharaletseng, litekanyetso tsa dopamine tsa moputso (Bohlale, 1978) kapa matlafatso (Fibiger, 1978). Litekanyetso tsa dopamine ka boeona e ne e le liphapang tse tsoang khopolong ea pele ea katecholaminergic, khopolo ea moputso oa noradrenergic (Stein, 1968). Tlhahlobo ea hona joale e senola se ka morao, karabelo ea pele, le boemo ba hona joale ba litekanyetso tse amanang le dopamine: dopamine hypothesis ea moputso, hypophesis ea dopamine ea matlafatso, le hypothesis ea anhedonia ea ketso ea neuroleptic.

Eya ho:

MAHLOMOLA

Khopolo ea hore boitšoaro ba liphoofolo bo laoloa ke moputso le kotlo e tsofetse ho feta nalane e tlalehiloeng (Plato o re ke moholoane oa hae). Khopolo ea hore mochine o sebetsang ka bokong o tšehetsa tšebetso ena e thehiloe ka kotloloho linthong tsa tlhaho ka ho fumana Olds and Milner (1954) hore likhoto li tla sebeletsa ho susumetsa motlakase oa tse ling empa eseng likarolo tse ling tsa bokapele ba letsoho. Sena se ile sa lebisa ho phatlalatsoeng ke Olds (1956) ea "litsi tsa boithabiso" ho lateral hypothalamus le libaka tse amanang le boko. Lithuto tsa ho hlohlelletsa boko ka Sem-Jacobsen (1959) 'me Heath (1963) o netefalitse hore batho ba tla sebeletsa ts'usumetso e joalo mme ba e thabela (Heath, 1972). Maqheku (Maqheku le maqheku, 1963) 'mapa oa boko ba likhoto bakeng sa libaka tsa meputso, hape joalo ka poleloana ea hae ea sehlooho "litsi tsa boithabiso" (Maqheku, 1956) e ne e hapa likelello tsa molokoana oa liithuti tseo a neng a sa nahane ka tsona ka litsi tse ikhethileng hoo e ka bang ka likarolo tse amanang tsa potoloho (Maqheku, 1956; 1959; Maqheku le maqheku, 1965). Olds (1956) ba nka hore ke lisekete tse ikhethang tse "ka thabisoang ke khotsofalo ea lintho tsa mantlha - tlala, thobalano, lenyora le tse ling."

Malebela a pele a seo li-neurotransmitters li ka bang le matšoao a amanang le moputso bokong bo tsoa lithutong tsa meriana. Olds le Travis (1960) 'me Stein (1962) e fumane hore tranquilizer e hlasimolla le ho chlorpromazine ka mokhoa o hlollang oa ho iphumanela, athe amphetamine e ne e e susumetsa. Imipramine e hlahisitse litlamorao tsa amphetamine (Stein, 1962). Reserpine e ne e tsejoa ho fokotseha noradrenaline ea bongo, chlorpromazine e ne e tsejoa ho thibela li-receptor tsa noradrenergic, amphetamine e ne e tsejoa e le renadrenaline renaser, mme imipramine e ne e tsebahala ka ho thibela ho khutlisa noradrenergic. Haholo-holo motheong oa lintlha tsena le sebaka sa libaka tsa moputso kamanong le lisele le likhoele tsa noradrenergic, Stein (1968) o khothalelitse hore ts'ebetso ea moputso e kopantsoe ke tsela ea methapo ea methapo ea methapo (e thabisang, qalong Stein o ile a supa sehlopha sa selefouno sa A10, se ileng sa fetoha dopaminergic ho fapana le neradrenergic neurons, joalo ka tšimoloho ea sistimi ena). Ha a ntse a pheta phetisetso ea hae, CD Bohlale le Stein (1969; 1970) e fumane hore inhibition ea dopamine-β-hydroxylase enzyme e fetolang dopamine ho norepinephrine - e felisitse boithati le ho felisa ketso e matlafatsang ea amphetamine; tsamaiso ea methapo ea l-norepinephrine e nchafalitse ho intša le ho khutlisetsa bokhoni ba dopamine ho e tsamaisa.

Nakong ea ho qaptjoa ha khopolo ea noradrenergic ea moputso, dopamine e ne e tsejoa e le setsi sa pele sa Noradrenergic empa eseng joalo ka sebui ka tokelo ea sona. Empa ka nako ena, Carlsson et al a. (1958) o khothalelitse hore dopamine e ka ba neurotransmitter ka tokelo ea eona. Ho sibolotsoe hore noradrenaline le dopamine li na le likarolo tse fapaneng tsamaisong ea methapo (Carlsson, 1959; Carlsson le Hillarp, ​​1962) e hlahile e tiisa taba ena, 'me libaka tsa meputso tikolohong ea lisele tse nang le "dopamine" tsa "midbrain" li ile tsa lebisa Crow le ba bang ho fana ka maikutlo a hore li-transmitter tse peli tsa catecholamine ho li-forebrain circry - noradrenaline le dopamine - e mong le e mosebetsi oa moputso (Crow, 1972; lla et al a., 1972; Phillips le Fibiger, 1973; Sejeremane le Bowden, 1974).

Bopaki bo ileng ba qetella bo felisitse karolo ea bohlokoa bakeng sa norepinephrine ho hlohlelletsang boko le moputso oa lithethefatsi tse lemalloang bo ile ba qala ho bokellana ho tsoa mehloling e 'meli: pharmacology le anatomy. Taba ea pharmacological e ne e le hore na bakhethoa ba noradrenergic blockers kapa depletions ba sitisa ts'ebetso ea moputso ka bo bona kapa ba sitisa matla a liphoofolo a ho sebetsa. Ka mohlala, Roll (1970) e tlalehile hore inadition ea noradrenergic e sitisitse boithati ka ho etsa hore liphoofolo li robala; ho ba tsosa ho khutlisitse boitšoaro ka nakoana, ho fihlela liphoofolo li robala hape (Roll, 1970). Lira tsa "receptor" tsa Noradrenergic li sentse ka mokhoa o hlakileng ho itšunya-tšunya ka mekhoa e khothalletsang tšilafalo ho fapana le ho lahleheloa ke kutloisiso ea moputso (Fouriezos et al a., 1978; Franklin, 1978). Hape, bahanyetsi ba noradrenergic ba sitiloe ho sitisa ho itaola ka mokhoa o ikemetseng (IV) oa ho iphelisa oa amphetamine (Yokel le Wise, 1975; 1976; Risner le Jones, 1976) kapa koae (de Wit and Wise, 1977; Risner le Jones, 1980). Ho feta moo, liso tsa likhoele tsa methapo ea methapo ea tsebe li ile tsa sitoa ho sitisa maikutlo a ho itlhasimolla ka li-electrodes tse tsosang takatso haufi le locus coeruleus, moo bundle e qalileng teng, kapa ho hypothalamus ea morao-rao, eo merero ea bongata (Corbett et al a., 1977). Qetellong, 'mapa oa sebaka ka hloko sa sebaka sa cousuleus le tšupa-nako ea likhoele tse qalileng moo li senotse hore libaka tse ntle tsa meputso libakeng tsena li ne li sa tsamaellane le sebaka se hlakileng sa likarolo tsa nalane tsa "Noradrenergic" (Corbett le Wise, 1979).

Ka lehlakoreng le leng, ha bahanyetsi ba khethiloeng ba li-dopamine receptors ba fumaneha, bopaki bo ile ba qala ho bokella hore dopamine receptor blockade e sitisitse ho ithorisa ka mekhoa e neng e fana ka maikutlo a ho phahamisa moputso ho e-na le tšenyo ea matla a ts'ebetso. Ho ne ho na le ts'oaetso e kholo ea pele ea hore phello ea bahanyetsi ba dopamine - neuroleptics - haholo-holo ts'enyo ea koloi (Fibiger et al a., 1976). Phuputso ea rona ea pele sebakeng sena e ne e se tlas'a Tlhaloso ena hobane ts'ebetso ea rona e ntlafalitsoe ho e-na le ho sitisoa ke li-neuroleptics. Lithutong tsa rona tsa ho ithuta li ile tsa koetlisetsoa ho hatisa mochini bakeng sa ente ea IV ea amphetamine, e leng lithethefatsi tse etsang hore ho lokolloe e 'ngoe ea li-neurotransmitter tse' ne - norepinephrine, epinephrine, dopamine le serotonin. Re koetlisitse liphoofolo ho ikatisa IV amphetamine mme ra phephetsa le bahanyetsi ba ikhethileng bakeng sa li-adrenergic kapa dopaminergic receptors. Liphoofolo tse tšoaroang ka tekanyetso e tlase le e leka-lekaneng ea li-dopamine antagonists li ile tsa eketsa feela karabelo ea tsona (joalo ka liphoofolo tse lekiloeng ka tekanyetso e tlase ho feta ea amphetamine), ha liphoofolo tse tšoaroang ka tekanyetso e phahameng li ile tsa eketseha ka hora ea pele kapa tse peli empa tsa arabela khafetsa kamora moo (joalo ka liphoofolo e lekoa ka saline e emisitsoeng bakeng sa amphetamine) (Yokel le Wise, 1975; 1976). Litlamorao tse tšoanang li ile tsa bonoa khatellong ea likhoto bakeng sa cocaine (de Wit and Wise, 1977). Litlamorao tse fapaneng haholo li ile tsa bonoa le bahanyetsi ba khethiloeng ba Noradrenergic; Lithethefatsi tsena li fokotsehile ho arabela ho tloha qalong ea seboka 'me ha lia ka tsa lebisa ho fokotseha ho feta ha liphoofolo li fumana le ho bona moriana o boemong bona (Yokel le Wise, 1975; 1976; de Wit and Wise, 1977). Keketseho ea ho arabela moputso oa lithethefatsi ho hlakile hore e ke ke ea hlahisoa ka lebaka la ts'enyehelo ea ts'ebetso. Liphumano li ile tsa hlalosoa e le ho bonts'a phokotso ea katleho e atlehang ea amphetamine le cocaine, e le hore nako ea moputso ho tsoa ka jekeng e fanoeng e fokotsehe ke dopaminergic, empa eseng noradrenergic, antagonists.

Tumellanong le lithuto tsa ramatiki tsa moputso oa matla a kelello. Mona, leha ho le joalo, bahanyetsi ba dopamine, joalo ka ho fokotsa meputso, ba fokotsoe ho fapana le ho hatella ka matla. Lebaka la hore li-neuroleptics li fokotsehe ho arabela bakeng sa ts'usumetso ea boko le ho eketsa ho arabela bakeng sa li-psychomotor tse hlasimollang li monate ebile li se li utloisisoa (Lepore le Franklin, 1992), empa ka nako eo ho fokotseha ho arabela ho ile ha khothalletsoa ho bonts'a litla-morao tsa parkinsonian tsa ho senyeheloa ke dopaminergic (Fibiger et al a., 1976). Lenane la nako leo re le fumaneng le ile la bonahala le hatisa tlhaloso ena. Re ile ra latela mokhoa oa nako oa ho araba liphoofolo tse koetlisitsoeng hantle tse ileng tsa phekoloa pele ka li-dopamine antagonists pimozide kapa butaclamol. Re fumane hore liphoofolo li arabela ka mokhoa o tloaelehileng metsotsong e 'ngoe le e' ngoe ea pele, ha li ka be li lebelletse moputso o tloaelehileng ho tsoa nalaneng ea matlafatso ea pejana, empa li ile tsa lieha kapa tsa emisa ho araba, ho latela lenane la li-neuroleptic, joalo ka ha liphoofolo li sa lekoa ka tlasa maemo a fokotsehile moputso (Fouriezos le Wise, 1976; Fouriezos et al a., 1978). Liphoofolo tse iketselitsoeng ka mohanyetsi oa Oradrenergic antagonist phenoxybenzamine, ka lehlakoreng le leng, li bonts'a khatello ea maikutlo ho tloha qalong feela ea thuto mme ha ba ka ba lieha ho feta ha ba ntse ba fumana le ho fumana khothatso e khotsofatsang. Ts'ebetso e ne e le mpe liphoofolong tse tšoaroang ke phenoxybenzamine, empa ha ea ka ea mpefala ha liphoofolo li fumana boiphihlelo ka moputso ha li ntse li le tlasa tšusumetso ea lithethefatsi.

Seo bahanyetsi ba dopaminergic empa e seng bo-Noradrenergic se sitisitse bokhoni ba moputso ba ho tsibosa karabelo e matlafalitsoeng se netefalitsoe ho liphoofolo tse lekoang tlhahlobo ea sephethe-phethe ea discrete. Mona, liphoofolo li ile tsa matha lebelo la limithara tse peli ho tloha lebokoseng la ho qala ho isa lebokoseng la sepheo moo li neng li ka tobetsa hona teng, tekong e 'ngoe le e' ngoe ea 10 ka letsatsi, bakeng sa koetliso ea halofo ea bobeli ea 15 ea halofo ea bobeli ea moputso oa ts'ebetso ea boko. Kamora matsatsi a 'maloa a ho ikoetlisa liphoofolo li ile tsa lekoa kamora ho hlohlona ha methapo ea methapo. Nakong ea liteko tsa 10 maemong a methapo ea kutlo, liphoofolo li ile tsa emisa ho tlohela lebokose la ho qala hang ha monyako o buloa, tsa emisa ho matha ka potlako le ka kotloloho lebokoseng la sepheo, 'me tsa emisa li hatella pele. Habohlokoa, leha ho le joalo, karabo e khotsofatsang - ha ba fumana ts'usumetso hang ha ba fihlella karabo ea lebokose la sepheo - ba senyehile pele ho likarabo tsa sesebelisoa - ba siea lebokose la ho qala 'me ba tsamaisa alleyway e senyehile. Liphoofolo li siile lebokose la ho qala ka latency e tloaelehileng bakeng sa liteko tsa 8 tsa pele, li matha ka tloaelo bakeng sa liteko tsa 7 tsa pele feela, 'me li hatelloa ka litekanyetso tse tloaelehileng bakeng sa liteko tsa 6 tsa pele feela tsa seboka sa liteko tsa neuroleptic. Kahoo liphoofolo li bontšitse matšoao a ho soetseha moputsong - ho bontšitsoe ke karabelo e fokotsehileng ka lebokoseng la sepheo - pele ba bontša ho haelloa ke ts'usumetso e bonts'itsoeng ka ho arabela.

Liphumano tsena tsa ho ikhatholla li ne li sa lumellane hape le monyetla oa hore litekanyetso tsa rona tsa neuroleptic li mpa li baka likotsi tsa koloi. Liphoofolo li ile tsa bonts'a bokhoni bo tloaelehileng qalong ea linako, 'me tsa tsoela pele ho matha ka lebelo ho fihlela kamora ho bontša matšoao a ho nyahama ka moputso o lebokoseng la sepheo. Ho feta moo, litekong tse ntseng li tsoela pele tsa tlhahlobo eo ka linako tse ling liphoofolo tse tšoaroang li-neuroleptic ka linako tse ling li tlohang liphapusing tsa tsona tsa liteko tse bulehileng ka holimo li bile li leka-lekane haufi le mabota a plywood; ka hona liphoofolo li ne li ntse li e-na le matla a tsamaeang hantle a koloi le tšebelisano (Fouriezos, 1985). Ho feta moo, liphoofolo tse tšoaroang ke neuroleptic tse ileng tsa khaotsa ho araba kamora metsotso e fokolang ha lia ka tsa etsa joalo ka lebaka la mokhathala; ba qale ho arabela ka mokhoa o tloaelehileng ha ba hlahisoa ke sepheo se lebelletsoeng la moputso oa tikoloho (Fouriezos le Wise, 1976; Franklin le McCoy, 1979). Ntle le moo, kamora ho tima karabo e le 'ngoe e ithutileng bakeng sa moputso oa ts'usumetso ea boko, litoeba tse tšoaroang ke methapo li tla qala, ka matla a tloaelehileng a karabelo, mokhoa o mong, o ithutileng pele, karabelo e matla bakeng sa moputso o tšoanang (ba ntan'o felisoa ka karabelo e tsoelang pele ea karabo ea bobeli: Gallistel et al a., 1982). Kamora nako, litekanyetso tse lekanang tsa moputso oa li-neuroleptics ha li qobelle siling e arabeloang joalo ka phetoho ea litlhoko tsa ts'ebetso (Edmonds le Gallistel, 1974); empa ba mpa ba eketsa palo ea monyaka (moputso) o hlokahalang ho susumetsa ho arabela ka litefiso tse phahameng tse tloaelehileng (Gallistel le Karras, 1984). Liphumano tsena tsa bo-ramahlale li bontšitse hore eng kapa eng eo e ka 'nang ea e-ba le bofokoli ba' nete, lithethefatsi tsa neuroleptic li senya katleho ea mehopolo ea ts'usumetso ea kelello le meputso e susumetsang ea psychomotor.

Tumellanong le lithuto tsa ramatiki, re qalile lithuto tsa 'mapa oa anatomical ka melemo e' meli ho feta mekhoa e fetileng. Pele, re sebelisitse elektrone e tsamaeang (Bohlale, 1976) hore re tle re leke libaka tse 'maloa tsa tšusumetso kahare ho phoofolo ka' ngoe. Ho phoofolo e 'ngoe le e' ngoe, ka hona, re ne re e-na le taolo ea "anatomical control": libaka tse sa sebetseng hantle tsa ho tsosa tse holimo kapa ka tlase ho loci moo ho hlohlelletsa ho neng ho fana ka moputso. Ho tsamaisoa ha li-elektrode tsa 1 / 8 mm hangata ho ne ho lekane ho nka ntlha ea elektrone ho tloha sebakeng sa ts'usumetso moo ho neng ho sa khothaletse sebaka sa sebaka seo e neng e le ho sona, kapa ka mokhoa o fapaneng. Sena se re lumelletse ho tseba meeli ea "dorsal-ventral" ea "" potry "meputso sebakeng sa phoofolo e 'ngoe le e' ngoe e emeng. Taba ea bobeli, re nkile monyetla ka mokhoa o mocha oa histochemical (Bloom le Battenberg, 1976) ho khetholla meeli ea lits'ebetso tsa catecholamine ho lisebelisoa tse tšoanang tsa nalane tse bonts'itseng pina ea electrode. Boithuto ba pejana bo ne bo ts'epile libakeng tsa elektrode e le ngoe ho phoofolo e 'ngoe le ho bapisoa pakeng tsa likarolo tsa nalane tsa lipale tsa nissl le lits'oants'o tsa mela tse bonts'a libaka tsa sistimi ea catecholamine. Lithuto tsa rona tsa 'mapa li bonts'itse hore meeli ea libaka tse sebetsang tsa ts'usumetso e ne e sa tsamaisane le meeli ea lihlopha tsa cell cell tsa noradrenergic kapa li-bundle tsa fiber (Corbett le Wise, 1979) 'me ea lumellana le meeli ea lihlopha tsa lisele tsa dopamine sebakeng se potoloho ea karolo ea bohlano le sebaka sa substantia nigra pars compacta (Corbett le Wise, 1980))Bohlale, 1981). Le ha mosebetsi o latelang o hlahisitse potso ea hore na ts'usumetso e ntle e ts'ebetso ea ts'ebetso ea catecholamine ka kotloloho kapa ho na le moo e kenya ts'ebetso li-fiber tsa bona tse tlase (Gallistel et al a., 1981; Bielajew le Shizgal, 1986; Li-yoom et al a., 1988), lithuto tsa 'mapa li ne li tloaetse ho lebisa tlhokomelo ho dopamine ho fapana le lits'ebetso tsa norepinephrine e le likarolo tse tlase tsa moputso.

Poleloana "anhedonia" e qalile ho hlahisoa kamanong le lithuto tsa moputso oa lijo (Ke bohlale et al a., 1978). Mona hape, re fumane hore ha liphoofolo tse koetlisitsoeng hantle li ne li qala ho hlahlojoa tlas'a tekanyetso e leka-lekaneng ea dopamine antagonist pimozide, li ile tsa qala ho arabela ka tloaelo bakeng sa moputso oa lijo. Ho joalo, liphoofolo tse iketselitsoeng ke pimozide li ile tsa arabela haholo (ho 0.5 mg / kg) kapa hoo e batlang e le tse ngata (ho 1.0 mg / kg) ka letsatsi la pele tlasa kalafo ea pimozide joalo ka ha li ne li fanoa ha lijo li fanoa ka lebaka la ho se pimozide. Ha ba qhekelloa ka matsatsi a mabeli ebe ba ea tlhahlobo ea bobeli tlas'a pimozide, leha ho le joalo, ba ile ba araba hangata ka karolo ea pele ea lithuto tsa bona tsa 45-min empa ba emisa ho araba pejana ho feta tloaelehileng mme karabelo ea bona ka botlalo bakeng sa thuto ena ea bobeli e ne e le tlase haholo ho feta ho letsatsi le senang lithethefatsi kapa ka letsatsi la bona la pele la tlhahlobo ea pimozide. Ha a ntse a leka le ho leka makhetlo a boraro le a bone tlasa pimozide, liphoofolo li ne li ntse li qala ho araba ka mokhoa o tloaelehileng empa li ile tsa emisa ho araba pejana. Ho arabela ka tloaelo metsotsong e 'maloa ea pele ea thupelo ka' ngoe ho netefalitse hore tekanyetso ea pimozide e ne e se feela ho nyenyefatsa liphoofolo; ea fokotseha ho arabela kamora ho latsoa lijo ka har'a boemo ba pimozide o khothalelitse hore phello ea moputso (e eketsang karabelo) ea lijo e anngoe hantle ha sisteme ea dopamine e koetsoe.

Phuputsong ena, sehlopha sa papiso se koetlisitsoe ka tsela e ts'oanang, empa liphoofolo tsena ha lia ka tsa putsoa ka matsatsi a mane a "liteko" ha lihlopha tsa liteko li ne li etelloa pele ka pimozide. Joalo ka ha liphoofolo tse phekotsoeng ka pimozide li ile tsa hatella makhetlo a 200 a tloaelehileng bakeng sa lipilisi tsa lijo ka letsatsi la pele, le liphoofolo tse sa fuoang moputso le tsona li ile tsa tobetsa makhetlo a makholo a 200 leha ho ne ho se na moputso o tloaelehileng oa lijo. Matsatsing a latellanang a liteko, leha ho le joalo, ho hatella ka lever sehlopheng se sa putsoang ho theohetse ho likarabo tsa 100, 50 le 25, ho bonts'a phokotso e lebelletsoeng ea ho hanyetsa pheliso e ts'oanang le mohlala o bonoang liphoofolong tse tšoaroang ke pimozide. Mokhoa o ts'oanang le liteko tse latellanang o bonoa ha liphoofolo tse koetlisitsoeng tlasa bohloki li lekoa makhetlo a 'maloa tlasa maemo a ho khora; lekhetlo la pele ha liphoofolo li lekoa le ho ja lijo tse neng li fumaneha ka bolokolohi pele kapa nakong ea tlhahlobo. Joalo ka khatello e tsamaisoang ke lever liphoofolong tsa rona tse phekotsoeng tsa pimozide kapa tse sa fuoeng moputso, ho ja ho khanneloang ke tloaelo ho fokotseha hanyane ka hanyane ka liteko tse phetoang. Morgan (1974) e bitsitse ho senyeha ho tsoelang pele ha ho arabela ka "khanyetso" ho khotsofatsa, ho lebisa tlhokomelo ho ho ts'oanang le ho hanyetsa pheliso. Maemong 'ohle a mararo - ho araba tlasa methapo ea kutlo, ho araba tlasa moputso, le ho arabela tlasa satiety - boits'oaro bo khannoa ke tloaelo ea karabelo e senyehang haeba e sa ts'ehetsoe ke matlafatso a tloaelehileng. Tekong ea rona, sehlopha se eketsehileng sa papiso se thehile hore ho ne ho se na litlamorao tse fokolisang tsa liteko tse phetoang ka pimozide, sethethefatsi se nang le halofo ea bophelo bo bolelele mme se ka tlisoa ke ho ts'oaroa ke mafura. Liphoofolo tsa sehlopha sena li ile tsa amohela pimozide ka masakeng a tsona empa ha lia ka tsa lekoa matsatsing a pele a mararo a "liteko"; ba ile ba lumelloa ho hatella bakeng sa lijo feela kamora letoto la bone la liente tsa pimozide. Liphoofolo tsena li ile tsa arabela ka cheseho bakeng sa lijo kamora kalafo ea tsona ea bone ea pimozide, joalo ka liphoofolo tse fuoeng monyetla oa ho hatella lijo ka lekhetlo la pele ha li phekoloa ka pimozide. Kahoo ho araba Teko ea 4 ho ne ho sa itšetleha feela ka ho ba le pimozide nakong e fetileng, empa le ho ba le eona latsoa lijo tlasa maemo a pimozide nakong e fetileng. Ho hong ho mabapi le mohopolo oa boiphihlelo ba lijo tlasa pimozide - eseng feela ea pimozide feela - ho bakile ho khaotsa ho arabela pejana ho neng ho bonoa ha liteko tsa pimozide li phetoa. Taba ea hore liphoofolo tse neng li entsoe ka pimozide li ile tsa amohela lijo ka cheseho ho fihlela kamora hore li li latsoe maemong a pimozide ho re lebisitse ho bolela hore lijo li ne li sa natefise tlasa maemo a pimozide. Karolo ea bohlokoa ea se neng se bonahala e le ho theola boleng ba moputso tlasa pimozide e ne e hapiloe pejana polelong ea George Fouriezos mabapi le liteko tsa rona tsa ho hlohlelletsa bokong: "Pimozide e ntša mamello ho volts."

Litaba tsa Pele

Polelo e hlophisitsoeng ea anhedonia e hlahile lilemo tse 'maloa ka mor'a lithuto tsa moputso oa lijo koranteng e ileng ea hatisa litlhaloso tsa lithaka hammoho le lipampiri tsa tlhahlobo (Bohlale, 1982). Likarolo tse peli ho tse tharo tsa litlhaloso tsa pele li hanyetse khopolo-taba kapa tsa etsa tlhahiso e 'ngoe (Bohlale, 1990). Boholo, mabaka a mantlha a khahlano le hypothesis ea mantlha a ipiletsa ho bofokoli ba koloi kapa tse ling tsa ts'ebetso (E holotsoe le Zec, 1982; Koob, 1982; Ho ts'oasa et al a., 1984; Ahlenius, 1985). Tsena e ne e le likhang tse lebisitsoeng ho fumaneng hore li-neuroleptics li bakile ts'ebetso e fokotsehileng bakeng sa moputso oa lijo kapa ts'ebetso ea ts'ebetso ea boko empa ha ea ka ea bua haholo ka taba ea hore methapo ea kutlo e sitisitse tlhokomelo ho e-na le ho qala ho araba. Ba boetse ba hloleha ho sebetsana le taba ea hore ha liphoofolo tse tšoaroang ke methapo ea kutlo li emisa ho araba li ka khutlisetsoa ka ho li hlahisa molemong oa pele oa moputso o boletsoeng esale pele (Fouriezos le Wise, 1976; Franklin le McCoy, 1979). Ebile lintlha tsena ha li lumellane le 'nete ea hore karabelo e joalo e khutliselitsoe ka boeona o felisitsoe ka mokhoa o hlakileng. Qetellong, ha ba ka ba sebetsana le 'nete ea hore li-neuroleptics li bakile puseletso ea eketseha ho hatella moputso bakeng sa moputso oa amphetamine le koae (Yokel le Wise, 1975; 1976; de Wit and Wise, 1977).

Bopaki bo qaqileng haholo bo khahlano le hypothesis ea motor bo ile ba hlakisoa pele ho polelo e hlophisitsoeng ea polelo ea anhedonia. Pampiri (Ke bohlale et al a., 1978) e ntse e qotsitsoe ka mokhoa o tsitsitseng, empa mohlomong e fumaneha seoelo hona joale. Liphumano tsa mantlha li akaretsitsoe ka holimo, empa li ntse li tsoela pele ho qoba ho hlokoa ke batšehetsi ba bangata ba li-hypotheses tsa motor (kapa litlatsetso tse ling tsa ho fokolisa); ka lebaka lena pampiri ea mantlha e ntse e lokela ho baloa. Liphetho tse tebileng ke hore litekanyetso tse itekanetseng tsa li-neuroleptics li latela hantle feela ho arabela lijo ka mor'a hore phoofolo e be le boiphihlelo ka lijo tseo ha e ntse e le tlasa khatello ea methapo ea kutlo. Haeba phoofolo e bile le tsebo ea methapo ea kutlo ha ho se na lijo, litlamorao tsa eona tsa ho arabela lijo li fokola; leha ho le joalo, kamora ho ba le boiphihlelo ka lijo tlasa ts'usumetso ea methapo, phello ea methapo ea kutlo e ba matla le ho feta. Litlamorao tse tšoanang li bonoa ha likarabo tsa 'mele tse hlokahalang feela ke tsa ho kha lijo, ho li hlafuna le ho li metsa (E bohlale ebile e kopane, 1984; Bohlale le Raptis, 1986).

Linyeoe tse 'maloa tsa liphoso tsa anhedonia e bile tse ngata haholo ho feta tse kholo. Ha ba ntse ba lumela hore litlamorao tsa li-neuroleptics li ke ke tsa hlalosoa e le tšilafalo ea makoloi, bangoli ba 'maloa ba khothalelitse mabitso a mang bakeng sa boemo bona. Katz (1982) e bitsoa "hedonic arousal"; Liebman (1982) e bitsoa "neuroleptothesia"; Rech (1982) e e bitsitse "neurolepsis" kapa "blunting of reactact reactivity"; Kornetsky (1985) e e bitsitse bothata ba "tsoho e susumetsang"; le Koob (1982) o kopile potso ka ho e bitsa bothata ba makoloi a "maemo a holimo". Linyefolo tse fapaneng li ne li bua ka mokhoa o fapaneng anhedonia hypothsis, mohopolo o matlafatsang, le mohopolo oa moputso.

Anhedonia

Khopolo-taba ea anhedonia e ne e hlile e lumellana le khopolo-taba ea hore dopamine e ne e le bohlokoa bakeng sa ts'ebetso e lekantsoeng ea moputso. Polelo ea pele ea khopolo-taba e ne e le hore neuroleptic pimozide "e bonahala e khetholla ka mokhoa o khethollang phello e khotsofatsang ea lijo le tse ling tse susumetsang"Bohlale, 1978). E ne e hlile e se khopolo-taba mabapi le anhedonia e nang le boiphihlelo empa e ne e le khopolo-taba mabapi le ts'ebetso e lekantsoeng ea moputso. Lekhetlo la pele khopolo-taba e ne e hlile e ngotsoe "anhedonia hypothesis" (Bohlale, 1982), ho boletsoe ka mokhoa o tjena: ) hangata e tsamaeang le thabo e ikhethang. ” Khopolo-taba e hokahantse ts'ebetso ea dopamine ka kotloloho ho tsosa le ho matlafatsa e matlafatsang - likarolo tse peli tsa bohlokoa tsa meputso - mme e fana ka maikutlo a kamano e le 'ngoe feela le boiphihlelo bo ikhethileng ba monyaka oo "hangata" o tsamaeang le ts'ehetso e nepahetseng.

Tlhahiso ea hore dopamine e ka ba ea bohlokoa bakeng sa boithabiso ka boeona e bile karolo ea litlaleho tsa subgential tsa bakuli (Healy, ka 1989) kapa lithuto tse tloaelehileng (Hollister et al a., 1960; Bellmaker le Wald, 1977) fuoa kalafo ea neuroleptic. Dysphoria e bakoang ke li-neuroleptics e lumellana hantle le tlhahiso ea hore ba fuoe menyaka e tloaelehileng ea bophelo. Tumellanong le maikutlo ana e ne e le lithethefatsi tse kang cocaine le amphetamine - lithethefatsi tseo ho nahanoang hore li lemalla bonyane ka karolo ka lebaka la phello eo li e bakang (Bijerot, 1980) - eketsa maemo a dopamine ea extracellular (seakhi et al a., 1962; Axelrod, ka 1970; Carlsson, 1970). Neuroleptic pimozide, mohanyetsi oa tlholisano ho dopamine receptors (le neuroleptic e sebelisitsoeng lithutong tsa rona tsa liphoofolo), ho tlalehiloe hore e ile ea fokotseha euphoria e hlahisitsoeng ke IV amphetamine ho batho (Jönsson et al a., 1971; Sethunya et al a., 1972).

Bokhoni ba li-neuroleptics ba ho thibela litlamorao tsa euphoria li botsoa ka motheo oa litlaleho tsa bongaka tse tsoelang pele tsa amphetamine le ts'ebeliso ea koae ho bakuli ba lefu la methapo-kutlo le ka lebaka la liphuputso tsa morao-rao mabapi le litlamorao tse tlisoang ke batho ba tloaelehileng ba nang le neuroleptic . Tlhahlobo ea bongaka ho thata ho e hlalosa ka lebaka la litloaelo tse tlatselletsang ho dopamine receptor blockade mme ka lebaka la phapang ea taolo ea lithethefatsi, lethal dose la neuroleptic, le ho latela kalafo nakong ea ts'ebeliso ea matla. Lipatlisiso tse sa tsoa laoloa tsa litlamorao tsa pimozide on amphetamine euphoria (Brauer le de Wit, 1996; 1997) le tsona li na le mathata. Taba ea pele, ho na le litaba tsa pimozide lethal dose: tekanyetso e phahameng ea bafuputsi ba pele e ne e le 20 mg (Jönsson et al a., 1971; Sethunya et al a., 1972), athe, ka lebaka la ho tšoenyeha ka litla-morao tsa extrapyramidal, tekanyetso e phahameng lithutong tsa morao tjena e ne e le 8 mg. Ho tšoenyang le ho feta ke phapang ea phekolo ea amphetamine pakeng tsa lithuto tsa pele le tsa morao tjena. Lithutong tsa mantlha, 200 mg ea amphetamine e ile ea fuoa kahare ho basebelisi ba kamehla ba amphetamine; lithutong tsa morao tjena, 10 kapa 20 mg e ile ea fuoa baithaopi ba tloaelehileng ka molomo ka har'a li-caps. Motho o tlameha ho ipotsa hore na baithaopi ba tloaelehileng ba ikutloa le ho lekola euphoria e tšoanang ho tsoa ho li-capsule tsa bona tsa 20 mg joalo ka ha ho utluoa ke basebelisi ba nang le amphetamine ba sa ts'oaneng ka mor'a ente ea 200 mg IV (Mosa, 2000; Volkow le Swanson, 2003).

Khopolo ea hore li-neuroleptics e tlisa thabo ea monehelo oa lijo le eona e qholotsoe motheong oa lithuto tsa litekete (Treit le Berridge, 1990; Pecina et al a., 1997). Mona phephetso e ne e ipapisitse le teko ea tatso ea tatso hape, haholo teko ea phello ea hedonic ea tatso e monate (Berridge, 2000). Teko e sebeliselitsoe ho phephetsa ka kotloloho khopolo-taba ea hore "pimozide le bahanyetsi ba bang ba dopamine ba hlahisa anhedonia, phokotso e ikhethileng ea bokhoni ba monyaka oa kutlo" (Pecina et al a., 1997, leq. EA-801-TL Phephetso ena, leha ho le joalo, e tlasa likhaohano tse tebileng: "Ha o sebelisa ts'ebetso ea tatso e le mokhoa oa 'ho rata' kapa tšusumetso ea hedonic ho bohlokoa ho hlaka ka pherekano e ka bang teng. Ts'ebeliso ea mantsoe a kang 'rata' le 'ho se rate' a joalo eseng ka hoo ho bolela hore litloaelo tse ntlafatsang tsa tatso li bontša a boiphihlelo bo tlisoang ke thabo e hlahisoang ke lijo ”(Berridge, 2000, leq. 192, ho hatisoa joalo ka ha ho ngotsoe qalong), le hore “Re tla beha 'ho rata' le 'ho batla' ka matšoao a qotsulo hobane ts'ebeliso ea rona e fapana ka tsela ea bohlokoa le ts'ebeliso e tloaelehileng ea mantsoe ana. Ka moelelo oa bona o tloaelehileng, mantsoe ana hangata a bua ka boiphihlelo bo ikhethileng ba monyaka kapa boikemisetso ba ho tseba ”Berridge le Robinson, 1998, leq. 313). Teko ea ts'ebetso ea tatso ea ts'ebetso e bonahala e le thata ho lekanya ka kotloloho monate oa lijo, kaha "mokhoa o tloaelehileng" oa ts'ebetso ea tatso ho paradigm ena o bonoa likhoto tse hlabang (Grill le Norgren, 1978) le karabelo tse tšoanang li bonoa ho bana ba anencephalic (Steiner, 1973). Kahoo ho bonahala eka tlhaloso ea pele ea teko ea ho hlophisoa ha tatso (Berridge le Grill, 1984) e ne e nepile: liteko li lekanya mekhoa e sa fetoheng ea ho kenella ha lijo kapa ho hana - haholo karolo ea ho metsa ho feta ea ho bososela - e bonts'a tšusumetso ea hedonic ha feela e bonts'a pherekano e ntle kapa e fosahetseng ea mokelikeli o kenngoeng molomong oa phoofolo e sa sebetseng.

Anhedonia vs Reforforced

Anhedonia hypothesis e ne e thehiloe tlhokomelong ea hore meputso e mengata e ile ea hloleha ho boloka maemo a tloaelehileng a ts'ebetso ea ts'ebeliso ea matla liphoofolong tse koetlisitsoeng hantle empa li le methapo. Sena ha sea ka sa nkuoa e le bopaki ba anhedonia ea neuroleptic, empa ho e-na le hoo ke bopaki ba ts'usumetso e ntle ea neuroloptic. Tlas'a kalafo ea neuroleptic liphoofolo li bontšitse ts'ebetso e tloaelehileng empa ho fokotseha ho tsoelang pele ho arabela ka hare le ka makhetlo liteko tse phetoang, mme litheko tsena li bapisoa le mohlala, haeba e se ka tekanyo, litheko tse ts'oanang tse bonoang liphoofolong tse neng li lumelloa feela ho arabela tlasa maemo a ho se moputsoKe bohlale et al a., 1978). Ho feta moo, likhoto tsa naïve li fumanoe li sa ithute ho tobetsa lijo ka mokhoa o tloaelehileng bakeng sa lijo haeba li entsoe ka li-neuroleptic bakeng sa lithuto tsa tsona (Bohlale le Schwartz, 1981). Kahoo, mokhoa oa ho itloaetsa lijo o atisoa haholo ke dopamine blockade. Liphumano tsena ha li na phephetso empa li bile li qotsitsoe ke bahlahlobisisi ba seo ho thoeng se bitsoa anhedonia hypothesis (Tombaugh et al a., 1979; Mason et al a., 1980), ba phehileng khang ea hore tlas'a maemo a bona li-neuroleptics li baka bofokoli ba tšebetso kaholimo le hofeta liphoso tse hlakileng tsa ts'ebetso. Ka lebaka la hore li-neuroleptics li thibela lits'ebetso tsohle tsa dopamine, tseo tse ling ho nahanoang hore li kenya letsoho ts'ebetsong ea makoloi, sena ha sea ka sa makatsa kapa sa hanyetsoa (Bohlale, 1985).

Ho ts'oana ho hlakileng lipakeng tsa litlamorao tsa ho se ruise moputso le litlamorao tsa moputso tlasa kalafo ea methapo ea kutlo li bontšoa hape ke paradigms tse peli tse poteletseng. Ea pele ke karolo e matlafatsang ea karohanyo. Ho thehiloe hantle hore liphoofolo li arabela haholoanyane tlasa maemo a ho timela haeba li koetlisitsoe hore li se lebelle moputso bakeng sa karabelo e 'ngoe le e' ngoe eo li e etsang. Hore liphoofolo li arabela ka mokhoa o fetelletseng haeba li koetlisitsoe tlasa matlafatso ea methapo li tsejoa e le phello ea matlafatso ea karolo (Robbins, 1971). Ettenberg le Camp ba ile ba fumana litlamorao tse matlafatsang tsa phetheho le mathata a methapo ea methapo ea mekhoa ea ho arabela le ho ikoetlisa ka metsi. Ba ile ba etsa liteko tsa liphoofolo nakong ea thupelo ka 'ngoe ho tse tharo. Lijo-kapa liphoofolo tse fuoang metsi li ile tsa koetlisoa, teko e le 'ngoe ka letsatsi, ho tsamaisa 155 cm ka tsela e otlolohileng ea lijo bakeng sa lijo (Ettenberg le Camp, 1986b) kapa metsi (Ettenberg le Camp, 1986a) moputso. Sehlopha se seng se koetlisitsoe tlasa kemiso e "tsoelang pele" ea ho tiisa; ke hore, ba amohetse moputso oa bona o khethiloeng ka matsatsi a 30 a koetliso. Sehlopha sa bobeli se ne se koetlisitsoe tlasa matlafatso a itseng; ba amohetse moputso oa bona o khethiloeng ka matsatsi a 20 ho a 30 a koetliso; matsatsing a 10 a arotsoe ka mokhoa o ikhethileng nakong ea thupelo, liphoofolo ha lia ka tsa fumana lijo kapa metsi ha li fihla lebokoseng la sepheo. Sehlopha sa boraro se ne se fumana lijo kapa metsi tekong e ngoe le e ngoe empa se ne se phekoloa nako le nako ka haloperidol ea neuroleptic; holima liteko tsa bona tsa koetliso tse 10 ba fumane lijo kapa metsi ka lebokoseng la sepheo, empa, ha ba se ba entsoe pele ka haloperidol matsatsing ao, ba ile ba fumana lijo kapa metsi tlasa maemo a thibelo ea dopamine receptor. Liphetho tsa mekhoa ena ea koetliso li ile tsa lekoa litekong tse 22 tsa "ho fela" ha letsatsi le letsatsi moo sehlopha ka seng se neng se lumelloa ho matha empa se sa fumane moputso ka lebokoseng la sepheo. Liphoofolo tsohle li ne li tsamaea butle butle ha liteko tsa ho timela li ntse li tsoela pele. Leha ho le joalo, ts'ebetso ea liphoofolo tse neng li koetlisitsoe tlasa maemo a matlafatso e ile ea mpefala ka potlako letsatsi le letsatsi ho feta ea liphoofolo tse neng li koetlisitsoe tlasa maemo a matlafatso. Liphoofolo tse neng li koetlisitsoe tlasa maemo a "a leeme" a haloperidol le tsona li ile tsa mamella ho feta liphoofolo ka koetliso e tsoelang pele ea matlafatso; liphoofolo tse kenang ka nakoana tsa haloperidol li ne li e-na le li-latency tsa mabokose a qalang le linako tse tsamaeang tse neng li ts'oana le tsa liphoofolo tse koetlisitsoeng tlasa matlafatso a itseng. Ka mantsoe a mang, liphoofolo li ile tsa itlhahisa ka haloperidol ka 1/3 ea matsatsi a tsona a koetliso li felisitsoe joalo ka ha eka ha li so fumane moputso ho 1/3 ea matsatsi a tsona a koetliso. Ha ho na monyetla oa ho ferekana mona, hobane pele ts'ebetso ea liphoofolo tse tšoaroang ke haloperidol e ne e le betere ho feta ea liphoofolo tse laoloang mme ea bobeli hobane haloperidol e ne e sa fanoe matsatsing a liteko, feela matsatsing a mang a thupelo.

Paradigm ea bobeli e poteletseng ke paradigm ea maoto a mabeli le khethollo ea lithethefatsi. Mona liphoofolo li koetliselitsoe ho tsoela pele li arabela ho e 'ngoe ea lolo e le ngoe ha feela lever e fana ka moputso oa lijo, le ho fetohela ho lever e' ngoe ha e sa fumane moputso. Ka litekanyo tse tlase tsa haloperidol, liphoofolo li fetohela habonolo ho lever e fosahetseng joalo ka ha li sa fumane lijo ka mochini oa tsona oa pele oa lever (Colpaert et al a., 2007). Ka mantsoe a mang, likhoto tse tšoeroeng ke haloperidol tse neng li fumana lijo mochineng oa tsona oa khatiso oa pele li ile tsa iketsa joalo ka likhoto tse tloaelehileng tse ileng tsa sitoa ho fumana lijo mochineng oa tsona oa khatiso. Sena e ne e se sesupo sa mofuta o mong oa bofokoli ba koloi ea haloperidol, hobane bopaki ba hore lijo ha li na phello tlasa haloperidol li ne li sa kenyeletse ho ba sieo ha karabelo empa ho e-na le hoo e ne e le ho qaleha ha karabo: karabelo ho mokoloto oa bobeli.

Kahoo ho hlakile ka ho hlaka hore, eng kapa eng eo ba e etsang, li-neuroleptics li fokotsa matlafatso ea meputso e mengata e tloaelehileng.

Matlafatso vs Ho Tsosa

Phephetso ea morao-rao ho hypothesis ea anhedonia e tsoa ho baruti ba pheha khang ea hore tšusumetso ea mantlha e hlahisoang ke li-neuroleptics ke tšenyo e kholo ho drive kapa sepheo sa ho fumana kapa ho fumana moputso ho fapana le ts'usumetso e tsamaeang le kamohelo ea moputso (Berridge le Robinson, 1998; Salamone le Correa, 2002; Robinson et al a., 2005; Baldo le Kelley, 2007). Tlhahiso ea hore dopamine e bapala karolo ea bohlokoa ts'usumetsong ea ts'usumetso e ne e hlile e hatelloa ka matla polelong ea mantlha ea anhedonia hypothesis ho feta anhedonia ka boeona: (a) bohlokoa bakeng sa boits'oaro bo tataisoang ke sepheo… ”(Bohlale, 1982). Hore bophahamo ba "extracellular dopamine" bo ka ts'ehetsa tatellano ea boits'oaro mohlomong bo bontšoa hantle ke "phello ea" priming "e bonoang ha moputso oa mahala o fuoa phoofolo eo ka nakoana e sa arabeleng mosebetsing oa seletsa (Howarth le Deutsch, 1962; Pickens le Harris, 1968). Tšusumetso ena e bontšoa hamolemo ke ho khutlisetsoa ka matla ke tšebeliso ea lithethefatsi ho liphoofolo tse fetileng liteko tsa ho timela khafetsa (Stretch le Gerber, 1973; de Wit le Stewart, 1983). E 'ngoe ea lisosa tse matla ka ho fetisisa tsa ho khutlisetsa ho arabela liphoofolong tse felisitseng mokhoa oa ho batla koae kapa tloaelo ea ho batla li-heroin ke ente e sa rutoang ea dopamine agonist bromocriptine (Ke bohlale et al a., 1990). Ho kenyelletsoa ha monate oa tšusumetso ke tšobotsi ea mantlha e khethollang mohopolo oa dopamine oa moputso ho tsoa ho hypophesis e fokolang ea matlafatso (Bohlale, 1989; 2004).

Le ha ho na le bopaki bo bongata ba hore dopamine e ka holisa kapa ea etsa hore motho a tsose takatso e matla, ho na le bopaki bo bongata ba hore lithethefatsi tsa "neuroleptic" ha li thibele takatso e tloaelehileng ea tlhaho e fuoang phoofolo e koetlisitsoeng hantle ka likeletso tse lemosang pele tikolohong. Joalokaha ho tšohliloe ka holimo, liphoofolo tse tšoaroang ke neuroleptic li tloaetse ho etsa tloaelo ea ho araba ka tloaelo. Liphoofolo tse joalo li qala empa ha se hangata li tsoelapele ho hatella, ho matha kapa ho jella ka likamoreng tse sebetsang, litselaneng tsa boipheliso kapa liteko tsa phepo ea mahala. Ha ho fanoa ka mosebetsi oa sephethe-phetho sa discrete, liphoofolo tse tšoaroang haloperidol li tsamaea hantle nakong ea teko ha haloperidol e fanoa; bofokoli ba bona bo matla bo hlaha feela ka le hlahlamang, ha haloperidol e se e entsoe tšebetso 'me sohle se setseng sa kalafo ke memori tekong ea kalafo (McFarland le Ettenberg, 1995; 1998). Likarolo tsa lebokose la ho qala li sitoa ho baka ho baleha ka tseleng ea lijo kapa li-heroin eseng ka letsatsi leo liphoofolo li le tlas'a tšusumetso ea haloperidol, empa ka letsatsi le hlahlamang ha ba hopola feela hore na moputso o ne o le joang ka letsatsi la haloperidol. Kahoo takatso e susumetsang ea phoofolo ka letsatsi leo e fumanang kalafo ea haloperidol ha e nyenyefatsoe ke kalafo; ho fapana le moo e tlameha ho ba mohopolo oa moputso o senyehileng o nyahamisang phoofolo letsatsi kamora teko ea kalafo. Ona ke ona molaetsa oa bohlokoahali ho tsoa lipatlisisong tsa litlamorao tsa methapo ea kutlo malebana le boits'oaro ba mesebetsi ea matsoho mefuteng ea mesebetsi; li-neuroleptics ka tekanyetso e nepahetseng ha li kena-kenane le bokhoni ba ho susumetsa ho ithuta ho hlohlelletsa boitšoaro bo susumetsang ho fihlela kamora hore maikutlo a qale ho felloa ke matla a ho boloka boitshwaro boo ka lebaka la boiphihlelo ba moputso maemong a methapo ya kutlo (Fouriezos le Wise, 1976; Fouriezos et al a., 1978; Ke bohlale et al a., 1978; Bohlale le Raptis, 1986; McFarland le Ettenberg, 1995; 1998).

Sena ha se bolele hore dopamine ha e na thuso ka botlalo boits'oarong bo susumetsoang, empa feela ke hore maqhubu a phasic dopamine a bakoang ke mophatlalatsi oa moputso (Schultz, 1998) are, hajoale, ha ho hlokahale bakeng sa tšusumetso e tloaelehileng ea liphoofolo tse nang le nalane ea ts'usumetso e sa kopaneng. Liphoofolo tse koetlisitsoeng hantle li arabela ntle le tloaelo, 'me li etsa joalo le tlas'a maemo a dopamine receptor blockade. Haeba dopamine ea boko ke feletseng Leha ho le joalo, ho na le litlamorao tse mpe tse mabapi le boitšoaro bo susumetsang (Ungerstedt, 1971; Stricker le Zigmond, 1974). Sena se bonahala ho tsoa lithutong tsa litoeba tse feto-fetohang tse sa kopanyeng dopamine; liphoofolo tsena, joalo ka liphoofolo tse nang le liteko tsa tšilafalo ea dopamine, li sitoa ho sisinyeha ntle le ha li tsosoa ke bohloko kapa khatello ea maikutlo, agonist ea dopamine, kapa caffeine ea dopamine e ikemetseng (dopamine-activant caffeine)Robinson et al a., 2005). Kahoo maemo a fokolang a dopamine a sebetsang a hlokahala bakeng sa boitšoaro bohle bo tloaelehileng; dopamine-liphoofolo tse felileng, joalo ka bakuli ba dopamine ba felisang lijo tse nang le li-parkinsonia (Hornykiewicz, 1979), li batla li sa sebetse ka botlalo ntle le haeba u hatelletsoe (Zigmond le Stricker, 1989). Har'a liphokotso tsa mantlha tse amanang le dopamine depletion ke litsgia le adipsia, tse nang le likarolo tse khothatsang le likarolo tsa makoloi (Teitelbaum le Epstein, 1962; Ungerstedt, 1971; Stricker le Zigmond, 1974). Melemo e thibelang moputso ea li-neuroleptics, leha ho le joalo, e hloleha ho hlahisa catalepsy e matla e bakoang ke ho tepella ho matla ha dopamine.

Accumbens vs Likarolo tse ling tsa Dopamine terminal

Tšimo ea dopamine terminal e amohetseng tlhokomelo e ngata mabapi le ts'ebetso ea moputso ke li-nucleus accumbens. Tlhokomelo e ile ea huleloa ho li-nucleus accumbens pele hobane liso tsa sena empa eseng litsamaiso tse ling tsa catecholamine li sitisitse ts'ebetso ea ts'ebetso ea cocaine (Roberts et al a., 1977). Tlhokomeliso e ngoe hape e hlahisitsoe ke litlhahiso tsa hore nucleus e bokelle septi e lokela ho nkuoa e le tlatsetso ea leoto la striatum, ho fapana le katoloso ea septum (Nauta et al a., 1978a,b) le hore ke khokahano lipakeng tsa tsamaiso ea maoto le methapo - e amanang le mesebetsi ea tšusumetso le maikutlo - le tsamaiso ea makoloi ea extrapyramidal (Mogenson et al a., 1980). Boithuto ba moputso oa opiate bo boetse bo khothalelitse hore ke sistamine ea mesolimbic dopamine - sistimi e rerang haholo ho tloha sebakeng sa tefo ea moea ho isa ho li-nucleus tse bokellanang - tse amanang le mosebetsi oa moputso. Morphine e sebakeng se sengoathoana sa moea e fumanoe e le ho kenya tšebetsong (Gysling le Wang, 1983; Matthews le Sejeremane, 1984), ka ho li hlakola (Johnson le North, 1992), dopaminergic neurons, le microinjections tsa morphine tikolohong ena li ka fuoa moputso oa ts'usumetso ea boko (Broekkamp et al a., 1976, e hlahisitsoeng ke maemo a khethiloeng a sebakaPhillips le LePiane, 1980), mme ba ne ba itlhomme pele ka tokelo ea bona (Bozarth le Bohlale, 1981).

Phephetso e ngoe ho li-hypopheses tsa dopamine ka lebaka leo e bile teng ka lebaka la ho fumana hore lesapo le bokellanang la lesapo la mokokotlo le sitoa ho senya boitšoaro bohle ba sebopeho sa lisebelisoa (Salamone et al a., 1997). Ntle le bothata ba hore ho ke ke ha khoneha ho hlahisa lesion nucleus accumbens ka boikhethelo mme, ka nako e ts'oanang, ka botlalo, ho na le mabaka a mang a ho nahana hore li-nucleus accumbens liso ha lia lokela ho felisa liketso tsohle tse susumetsang tsa dopamine. Taba ea mantlha, k'hok'heine e itšebetsa ka kotloloho eseng feela ho li-nucleus accumbens (Carlezon et al a., 1995; Kemoto, 2003), empa hape - hape ka cheseho - ka har'a methapo ea methapo e tlang pele ho nako (Goeders le Smith, 1983; Baeti et al a., 1986) le tuber FunKemoto, 2003). Moputso o kopantsoeng oa koae ha o fumanoe feela ke li-microinjection tsa D1 antagonist kahare ho sebaka sa karolelano ea mokokotlo (Ranaldi le Wise, 2001) empa hape ka liente tse tšoanang ho "antianti nigra "Quinlan et al a., 2004). Kamora nako, tokollo ea dopamine ea morao-rao ho dorsal striatum e ntlafatsa kopanya ea ho ithuta le ho hopola (Bosoeu le Viaud, 1991), le dopamine blockade sebakeng sa dorsal striatum e senya bokhoni ba nako e telele (mohlala oa cellular oa ho ithuta le ho hopola) sebakeng sena (Karolo ea tšepe et al a., 2001). Moelelo oa matlafatso ea memori ke hore, moelelo oa matlafatso (Landauer, 1969) le dopamine e bonahala e kopantsha mohopolo oa memori ho dorsal striatum le likarolo tse ling tse fapaneng (Bosoeu, 1989; Bohlale, 2004).

Kahoo, ka mabaka a fapaneng, "dopamine hypothesis" ha ea lokela ho fokotsoa ho "hypothesis" ea nucleus. Li-nyuklea tsa nyutlelie ke karolo e le 'ngoe ea masimo a dopamine a phethellelitsoeng mosebetsing oa moputso.

Litaba tsa Hona joale

Le ha bopaki bo ntse bo bokelletse butle-butle bakeng sa karolo ea bohlokoa ea dopamine ts'ebetsong ea moputso eo karolo eo re neng re e akaretse ka mokhoa o hlephileng e le "ts'usumetso e susumetsang" kutloisiso ea rona ea mofuta o nepahetseng oa ts'ebetso ena e ntse e tsoela pele ho nts'etsapele ka bolotsana le ho rarahana. Litaba tse 'ne, ntle le phapang ea khopolo-taba ea khale, li hlahile lingoliloeng tsa morao tjena.

Khothatso kapa Boiteko?

Tlhahiso e le 'ngoe, e fanoeng e le phephetso e tobileng ho hypothesis ea anhedonia le hypophesis ea dopamine ea moputso (Salamone et al a., 1994; 1997; 2005) ke hore se fokotsang methapo ea kutlo ha se susumetse kapa ho matlafatsa empa ke boikemisetso ba phoofolo ba ho ikitlaetsa (Salamone et al a., 2003). Tlhahiso ena ke semorahali feela. Ho ikemisetsa ho ikitlaetsa ke moelelo oa seo re se bolelang ka tšusumetso kapa ho khanna, karolo ea pele polelong ea likarolo tse tharo ea polelo ea anhedonia (Bohlale, 1982).

E ea Hloka Kapa e Lekane?

Boithuto ba litoeba tse feto-fetohang tsa dopamine ho dopaminergic neurons (empa ho bo boloka ka li-neurons tsa "Noradrenergic") li bonts'a hore dopamine ea boko ha e hlokehe ka botlalo bakeng sa ho ithuta ka sesebelisoa se fuoeng lijo. Haeba ba fuoa caffeine ho ba tsosa, litoeba tse haelloang ke dopamine li ka ithuta ho khetha letsoho le nepahetseng la T-maze bakeng sa moputso oa lijo (Robinson et al a., 2005). Sena se tlama dopamine ka har'a mouoane o khothalletsoang o haellang litakaneng tse haelloang ke dopamine tse sa phekoloeng ka koae, mme o bonts'a hore dopamine ha e bohlokoa ho - leha e le hore ka tloaelo e kenya letsoho haholo ho - litlamorao tse hlahisang lijo. Hoa thahasellisa ho hlokomela, leha ho le joalo, hore caffeine - e hlokahalang haeba litoeba tse feto-fetohang li ka phela ntle le dopamine - e boetse e khutlisa karabelo e felang e lahlehang kamora ho ruruha ha methapo ea methapo ea methapo ea methapo ho dopamine neurons ho liphoofolo tse kholo (leha ho le joalo)Sethoto et al a., 1977). Mokhoa oa litlamorao tsa k'hafeine ha o utloisisoe ka botlalo, empa caffeine e ama li-neuron tse tšoanang le tse bohareng tse tšoanang le litebello tse tloaelehileng tsa methapo ea methapo ea dopaminergic ea methapo ea methapo ea methapo ea methapo. E sebetsa moo e le phosphodiesterase inhibitor e eketsang intracellular cyclic AMP (Greengard, 1976) hammoho le mohanyetsi oa adenosine receptor antagonist (Snyder et al a., 1981). Ho feta moo, li-receptor tsa adenosine tse koetsoeng ke caffeine ka tloaelo li theha li-heteromers tse nang le dopamine receptors mme li ama karabelo e kenelletseng ho litlamorao tsa dopamine li-receptors tseo (Ferre et al a., 1997; Schiffmann et al a., 2007). Tšebelisano e rarahaneng ea dopamine le li-receptor tsa adenosine ka har'a striatum e hlahisa monyetla oa hore caffeine e nolofalletse ho ithuta ho litoeba tse haelloang ke dopamine ka ho nka sebaka sa dopamine ka har'a Cascade e arolelanoang kapa e fetang.

Moputso Kapa Phello ea Pono?

Schultz le basebetsi-mmoho ba bonts'itse hore li-neuronom tegmental dopamine neurons tse kentsoeng tšebetsong ea moputso ha li arabe moputso oa lijo feela, empa ka lebaka la boiphihlelo, ho ba boletseng ka moputso oa lijo (Romo le Schultz, 1990; Ljungberg et al a., 1992). Ha phoofolo e ithuta hore e hlohlelletsa tikoloho e hakanya moputso oa lijo, 200 millisecond burst of dopaminergic nerve fense eo pele e neng e baka ts'ebetso ea lijo ka boeona e hokahana, ho e-na le hoo, le tšusumetsong ea lijo e boletsoeng esale pele. Haeba tšusumetso ea lijo e reretsoeng ho rerela lijo ka karoloana feela ea liteko, ke moo dopaminergic neurons e phatlohang, ho isa tekanyong e tlase, ha e arabela mofetoleli le lijo; Ha matla a ho bolela lintho esale pele a matla le ho feta, karabelo e matla ho ea boletsoeng esale pele e ba le karabelo e fokolang tsebong ea lijo.

Taba ea hore li-neuron tsa dopaminergic e khaotsa ho arabela lijong ka boeona mme e arabela ho baetsi ba lijo esale e tsosa taba ea hore na tatso ea lijo ka bo eona ha e bolele feela esale pele bakeng sa moputso (Bohlale, 2002). Litakatso tse ling li shebahala e le tse matlafatsoang ntle le tšebeliso ho tloha ho tsoalo (Steiner, 1974), empa ba bang ba fumana bohlokoa bo susumetsang ka ho kopanya tatso ea bona le litlamorao tsa bona tsa ho kenyelletsa (Sclafani le Ackroff, 1994).

Dopamine le "Ho hatakela."

Khopolo ea "matlafatso" ke mohopolo oa "ho hatakela" mekhatloThorndike, 1898). Hore na mokhatlo o lipakeng tsa boemo bo itseng le tšusumetso e se nang litekanyetso (Pavlov, 1928), se susumetsang le karabelo (Thorndike, 1911), kapa karabelo le sephetho (Skinner, 1937), Matlafatso e bolela ho matlafatsoa ha kopano ka boiphihlelo. Mokhoa o mong oa ho e sheba ke hore matlafatso ke ts'ebetso e ntlafatsang kopanyo ea mohopolo oa memori bakeng sa mokhatlo (Landauer, 1969). Boithuto ba ts'ebetso ea dopaminergic ea morao-rao e bonts'a hore dopamine e sebeletsa ho ntlafatsa kapa ho tiisa mohopolo oa memori bakeng sa liketsahalo le mekhatlo e sa tsoa ba le tsebo, le hore o etsa joalo maemong a fapaneng a dopamine terminal (Bosoeu le Milner, 1992). Lintlha tse 'maloa (Reynolds et al a., 2001; Bohlale, 2004; Hyman et al a., 2006; Boholo et al a., 2007) joale fana ka karolo ea modulatory bakeng sa dopamine mefuteng ea cellular ea ho ithuta le ho hopola e lumellanang le maikutlo a hore dopamine e bapala karolo ea bohlokoa ho matlafatsong.

Eya ho:

KHAUHELO STATUS

Le ha phapang ea anhedonia hypothesis kapa dopamine hypotheses ea moputso kapa matlafatso e ntse e tsoela pele ho hlaha, khopolo-taba joalokaha e boletsoe qalong e ntse e ama maemo a ho kenyelletsa dopamine mohopolong oa tšusumetso. Maemo a tloaelehileng a dopamine ea boko a bohlokoa bakeng sa tšusumetso e tloaelehileng, ha maemo a phahameng a dopamine a bapala karolo ea bohlokoa ho matlafatso e thehang mekgwa ea karabelo le litempe ho kopanong lipakeng tsa meputso le tlhoko ea ho bolela esale pele. Monate oa subjential ke mokhoa o tloaelehileng oa liketsahalo tse thabisang tse bakang maemo a phahameng a phasic dopamine, empa liketsahalo tse sithabetsang le tsona li ka baka maemo a phahameng a dopamine; ka hona monyaka ha se sehokelo se hlokahalang sa ho phahamisoa ha dopamine kapa ho itšireletsa (Kelleher le Morse, 1968).

Eya ho:

References

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