Ho lemalla: Mafu a ho ithuta le ho hopola (2005)

Maikutlo: Ke botekgeniki empa e ngotsoe hantle ho feta lingoloa tse ngata tsa lipatlisiso. O pheta pale ea bokhoba joaloka ho ithuta ho feta tekano, e nkelang menyaka le litakatso tsa rona tsa tlhaho sebaka.


Steven E. Hyman, MD Am J Psychiatry 162: 1414-1422, Phato 2005

inahaneloang

Haeba neurobiology e tlil'o kenya letsoho kholisong ea kalafo e atlehileng ea ho lemalla lithethefatsi, bafuputsi ba tlameha ho fumana mekhoa eo lifaele tse batlang lithethefatsi li kopantsoeng ho sebelisoa ka mokhoa o qobelloang, mekhoa e tlatselitseng bothateng bo telele ba ho khutlela bothateng, le mekhoa eo ka eona litloaelo tse amanang le lithethefatsi li laola boitšoaro. Bopaki maemong a sekhahla sa limolek'hule, lits'ebetso, boits'oaro, le litekanyo tsa ho lekola li ntse li fetoha ho fana ka maikutlo a hore temallo e emetse tšebeliso ea methapo ea mekhoa ea ho ithuta le ho hopola e tlasa maemo a tloaelehileng a sebopeho sa boitšoaro bo amanang le ho phehella. meputso le likeletso tse ba bolelang esale pele. Sengoli se akaretsa bopaki bo fetohang sebakeng sena mme o phahamisa lipotso tsa bohlokoa tse setseng

Ho lemalla joala ho hlalosoa e le tšebeliso e mpe ea lithethefatsi leha e le litlamorao tse mpe. Lipakane tsa motho ea lemalloang li lieha ho fumana, ho sebelisa, le ho fola lithethefatsi, leha a sa atleha mesebetsing ea bophelo, bokuli, kotsi ea ho kenngoa chankaneng le mathata a mang. Tšobotsi ea bohlokoa ea ho lemalla ke ho phehella ha eona ka manganga (1, 2). Leha batho ba bang ba ka emisa ts'ebeliso e qobelloang ea koae, joala kapa lithethefatsi tse seng molaong ka bo bona, ho palo e kholo ea batho ba pepesetsoeng ts'enyo ea liphatsa tsa lefutso le tseo e seng tsa tlhaho (3-5), bokhoba ba motho bo ipaka ho ba bocha hape (2). Bothata bo ka sehloohong kalafong ea bokhoba ba tahi ke hore le kamora nako e telele ea ho se sebetse lithethefatsi, hantle kamora hore letšoao la ho khaola le fokotsehe, kotsi ea ho khutlela morao, hangata e hlahisoang ke lithahasello tse amanang le lithethefatsi, e lula e le holimo haholo. (6, 7). Ha ho ne ho se joalo, kalafo e ka kenyelletsa feela ho koala batho ba lemaletseng sebakeng se sireletsehileng ho fihlela matšoao a ho ikhula a le ka mor'a bona, a fana ka temoso e matla mabapi le boits'oaro ba kamoso, mme a qetile ka eona.

Khaello ea memori e lula e nkuoa e le maemo a kenyelletsang ho lahleheloa ke mohopolo, empa ho thoe'ng haeba boko bo hopola lintho tse ngata haholo kapa li le matla li rekota mekhatlo ea methapo? Lilemong tse leshome tse fetileng, tsoelo-pele ea ho utloisisa karolo ea dopamine thutong e amanang le moputso (8) ba entse nyeoe e qobelloang ea mohlala oa "ho ithuta ka methapo" o lumellanang le maikutlo a nako e telele mabapi le boitšoaro ba batho ba lemaletseng lithethefatsi. (6). Mosebetsi ona, hammoho le likhakanyo tsa morao-rao tsa computational tsa dopamine (9, 10), e khothalelitse mekhoa eo lithethefatsi le tšusumetso e amanang le lithethefatsi li ka fumanang matla a tsona a susumetsang. Ka nako e ts'oanang, lipatlisiso tsa cellular le tsa molek'hule li senotse ho tšoana pakeng tsa liketso tsa lithethefatsi tse lemalloang le mefuta e tloaelehileng ea ho ithuta le ho hopola (11-14), ka lehae la tsebo ea rona ea hona joale ea hore na memori e kentsoe joang (15) le hore na e phehella joang (15, 16) ha e hole le mokhoa o mong le o mong oa ho hopola oa mammary. Mona ke pheha khang ea hore ts'ebeliso ea tlhekefetso e emetse ts'ebetso ea methapo ea kutlo le mehopolo eo ka tlasa maemo a tloaelehileng e sebopang boitšoaro bo amanang le ho phehella meputso le mekhoa e ba boletseng esale pele. (11, 17-20).

Pholoho ea motho ka mong le ea mefuta e batla hore lintho tse phelang li fumane le ho fumana lisebelisoa tse hlokahalang (mohlala, lijo le bolulo) le menyetla ea ho nyalana ho sa natsoe litšenyehelo le likotsi Lipheo tse joalo tsa tlholeho tse amanang le pholoho li sebetsa e le "meputso," ke hore, li lateloa ka tebello ea hore ts'ebeliso ea bona (kapa qetello) e tla hlahisa litholoana tse lakatsehang (ke hore, "li tla ntlafatsa lintho"). Boitšoaro bo nang le lipheo tse putsang bo tloaetse ho phehella ka matla ho fihlela sephetho le ho eketseha ha nako e ntse e feta (ke hore, lia matlafatsa) (21). Mekhatlo e khothatsang ea kahare, joalo ka tlala, lenyora, le ho tsosa takatso ea thobalano, e eketsa boleng ba khothaletso ea lintlha tse amanang le sepheo le lintho tsa sepheo ka bo bona le ho eketsa thabo ea tšebeliso (mohlala, lijo li natefeloa ha motho a lapile) (22). Litloaelo tsa kantle tse amanang le meputso (tšusumetso ea khothalletso), joalo ka pono kapa monko oa lijo kapa monko oa mosali e motona, li ka qala kapa tsa matlafatsa linaha tse susumetsang, tsa eketsa menyetla ea boits'oaro bo thata le bo thata ba boits'oaro, joalo ka ho cheka kapa ho tsoma lijo, li tla phethoa ka katleho, leha li tobane le litšitiso. Mekhoa ea boits'oaro e kenyelletsang ho fumana meputso e lakatsehang (mohlala, tatellano e amehang ho tsomeng kapa ho fumaneng) e fetisoa haholo. Ka lebaka leo, lipina tse rarahaneng tsa ts'ebetso li ka etsoa hantle le ka mokhoa o nepahetseng, joalo ka ha semathi se ithuta boits'oaro ho isa boits'oarong empa se ntse se fetoha habonolo ho arabela maemong a mangata a maemo. Litaba tse joalo tsa boitšoaro tsa pele-pele, tse iketselitsoeng le tsona li ka qalisoa ke mekhoa e boletsoeng esale pele ea moputso (19, 23).

Lithethefatsi tse lemalloang li fana ka maikutlo a boitšoaro bo hopotsang ba meputso ea tlhaho, leha mekhoa ea boits'oaro e amanang le lithethefatsi e khetholloa ke matla a bona a ho fetisa lipheo tse ling kaofela. Joalo ka moputso oa tlhaho, lithethefatsi li batloa ka tebello ea litholoana tse ntle (ntle le nnete e kotsi), empa ha batho ka bomong ba oela bothateng, ho batla lithethefatsi ho nka matla hoo ho ka susumetsang batsoali ho hlokomoloha bana, bao pele e neng e le ba tloloang molao ho etsa litlolo tsa molao. , le batho ba nang le maloetse a bohloko a amanang le joala kapa a tsubang ho tsuba le ho tsuba (24). Ka ho nka lithethefatsi tse pheta-phetoang ho tla litloaelo tsa homeostatic tse hlahisang ho its'etleha, tseo maemong a joala le li-opioidite li ka lebisang ho tloheng hoa syndromes tse tlisoang ke ho khaotsa lithethefatsi. Ho tlohela, haholo-holo karolo e amehang, ho ka nkuoa ho etsa naha e susumetsang (25) mme ka hona e ka fetisoa ho tlala kapa lenyora. Le ha ho qoba kapa ho khaotsa matšoao a ho khaotsa ho eketsa ts'usumetso ea ho fumana lithethefatsi (26), ho itšetleha le ho ikarola ha ho hlalose bokhoba (7, 19). Mehlaleng ea liphoofolo, ho khutlisetsoa ha lithethefatsi ka mor'a ho tlohela lithethefatsi ho susumetsoa haholo ke ho itlhahisa hape ka moriana ho fapana le ho tlohela. (27). Mohlomong ka mokhoa o tebileng le ho feta, ho ts'epa le ho tlohela ho ke ke hoa hlalosa tšekamelo e ts'oanang ea ts'oaetso ea ho khutla hape ka mor'a nako e telele ea ho tlohela thipa (6, 7, 19).

Ho oela hape kamora ho tlohela detox hangata ho laeloa ke litloaelo tse kang batho, libaka, paraphernalia, kapa maikutlo a 'mele a amanang le tšebeliso ea lithethefatsi pele. (6, 7) hape le ka khatello ea maikutlo (28). Lihormone tsa khatello ea maikutlo le khatello ea maikutlo tse kang cortisol li na le phello ea 'mele tseleng ea moputso, empa hoa thabisa ho tseba hore khatello ea maikutlo le lithethefatsi tse tlatsetsang ke bokhoni ba ho baka ho lokolloa ha dopamine. (28) le ho eketsa matla a li-synapses tse thabisang ho li-dopamine neurons sebakeng sa ventral tegmental (29). Ces li kenya ts'ebeliso ea lithethefatsi (11, 30), ho batla lithethefatsi (19, 31), le ts'ebeliso ea lithethefatsi. Sebaka sa thekiso ea lithethefatsi / se batlang lithethefatsi se entsoeng ke lithethefatsi se amanang le lithethefatsi se tlameha ho fetoha habonolo hore se atlehe lefatšeng la 'nete, empa ka nako e ts'oanang, ba tlameha ho ba le boleng bo phahameng haholo ba thuto le bo ikatisang haeba ba tla sebetsa hantle (19, 23, 31). Kannete ts'ebetso e itšetlehileng ka cue ea ts'ebetso ea lithethefatsi tse iketselitsoeng e entsoe hore e phethe karolo e kholo ho khutlisetsang ts'ebetsong hape (18, 19, 23).

Takatso e kenelletseng ea lithethefatsi ke sesupo sa ho tseba lithethefatsi; Litakatso tse kenelletseng li ka fanoa feela kapa ba nang le boiphihlelo bo matla haeba lithethefatsi li sa fumanehe habonolo kapa haeba motho ea lemaletseng a leka ho fokotsa tšebeliso. (19, 23, 31). Ke potso e bulehileng hore na takatso ea lithethefatsi tse kenelletseng, ho fapana le lits'ebetso tse susumetsoang, tse ikhethileng haholo, e bapala karolo ea mantlha ea ho batla lithethefatsi le ho ts'oara lithethefatsi. (32). Ho joalo, batho ka bomong ba ka batla le ho ipehela lithethefatsi le ha ka boikemisetso ba bona ba ikemiselitse ho se hlole ba etsa joalo hape.

Boemong ba laboratori, tsamaiso ea lithethefatsi (33, 34) le likotsi tse amanang le lithethefatsi (35-37) li bontšitsoe ho hlahisa litakatso tsa lithethefatsi le likarabo tsa 'mele tse kang ts'ebetso ea ts'ebetso ea methapo ea kutloelo-bohloko. Le ha tumellano e felletseng e sa tla hlaha, lithuto tse sebetsang tsa neuroimaging li tlalehiloe ka ts'ebetso ho arabela litheko tsa lithethefatsi ho amygdala, anterior cingulate, orbital pele le dorsolateral preortal cortex, le li-nucleus.

Dopamine Hypothesis

Mosebetsi o moholo oa ts'ebetso, ho kenyelletsa lithuto tsa pharmacological, lesion, transgenic, le micodialysis, o thehile hore thepa e khotsofatsang ea lithethefatsi tse lemalloang e itšetleha ka bokhoni ba tsona ba ho eketsa dopamine ho li-synapses tse entsoeng ke li-neurons tsa sebakeng sa midbrain ventral tegmental sebakeng sa li-nucleus (38-40), e lulang sebakeng sa "potral striatum", haholo-holo kahare ho bokaholimo ba khubung ea nucleus (41). Ventral tegmental tegmental sebakeng seo dopamine e nahanang ho ea libakeng tse ling tsa letsoalo tse kang pele ho cortex le amygdala le tsona li bapala karolo ea bohlokoa ho fetoleng boits'oaro ba ho sebelisa lithethefatsi. (42).

Lithethefatsi tse tlatsetsang li emela malapa a fapaneng a lik'hemik'hale, ho hlohlelletsa kapa ho thibela litebello tse fapaneng tsa pele tsa limolek'hule, mme li na le liketso tse ngata tse sa amaneng le kantle ho potoloho ea likarolo tsa methapo ea methapo / li-circus, empa ka mekhoa e fapaneng (mohlala, bona litšupiso 43, 44), kaofela qetellong li eketsa dopamine ea synaptic kahare ho li-nucleus accumbens. Leha e le karolo ea eona ea mantlha, dopamine ha se pale e felletseng bakeng sa lithethefatsi tsohle tse lemaletseng, haholo-holo li-opioids. Ntle le ho baka ho lokolloa ha dopamine, li-opioids li ka sebetsa ka kotlolloho bokong ba nko ho hlahisa moputso, mme norepinephrine e ka bapala karolo ea litlamorao tse thabisang tsa li-opioids hape. (45).

Mosebetsi oa morao-rao litekanyetso tsa boits'oaro, tsa 'mele, tsa maiketsetso le tsa limolek'hule li se li qalile ho hlakisa mekhoa eo ts'ebetso ea dopamine ka har'a li-nucleus li bokellanang, preortal cortex, le likarolo tse ling tsa forebrain li ka phahamisang ts'usumetso ea ts'ebeliso ea lithethefatsi ho isa moo matla a ho laola ts'ebeliso ea lithethefatsi e lahlehile. Mabaka a mabeli a bohlokoa a ho hlahloba lipatlisiso tsena ke hore ho lula ho le bolotsana ho eketsa seo re ithutang sona ho tsoa liphoofolong tse tloaelehileng tsa laboratori ho fihlela maemo a rarahaneng a batho a kang ho lemalla le hore ha ho na mohlala oa phoofolo ea ho lemalla o ka botlalo o tlisang matšoao a motho. Ho thoe, lilemo tse 'maloa tse fetileng li tlisitse tsoelo-pele ea bohlokoa ho fuputseng pathogenis ea ho lemalla.

Ketso ea Dopamine: Reward Prediction-Error Hypothesis

Morero oa dopamine ho tloha sebakeng sa ho kenella ka mokokotlo ho ea sebakeng sa nyutlelie ke karolo ea bohlokoa ea potoloho ea moputso oa boko. Potoloho ena e fana ka chelete e tloaelehileng bakeng sa ho baballa meputso e fapa-fapaneng ke boko (21, 46). Sebakeng sa "potop tegmental sebakeng" / "nucleus" e kenellang potoloho, dopamine e hlokahala bakeng sa ts'usumetso ea tlhaho, joalo ka lijo le menyetla ea ho tlolelana le liphoofolo, hore e be le moputso; ka ho tšoanang, dopamine ea hlokahala bakeng sa lithethefatsi tse lemalloang ho hlahisa moputso (22, 39, 40, 47). Phapang e totobetseng haholo pakeng tsa lintho tsa sepheo sa tlhaho, joalo ka lijo, le lithethefatsi tse tlatsetsang ke hore litlamorao ha li na bokhoni ba ho fana ka tlhoko ea tlhaho. Leha ho le joalo, hobane lithethefatsi tse lemalloang le meputso ea tlhaho e lokolla dopamine bokong ba li- nucleus le methapo e meng ea phatla ea morao-rao, lithethefatsi tse lemalloang li etsisa litlamorao tsa meputso ea tlhaho mme ka hona e ka baka boitšoaro (9, 22, 23). Ho joalo, ho 'nile ha nahanoa hore lithethefatsi tse lemalloang li na le monyetla oa tlholisano ho feta tšusumetso ea tlhaho ka hore li ka hlahisa litekanyetso tse kholo haholo tsa dopamine le ts'usumetso ea nako e telele ho feta.

Ke tlhahisoleseling efe e kentsoeng ke ho lokolloa ha dopamine? Pono ea pele ea ts'ebetso ea dopamine e ne e le hore e sebetsa e le sesupo sa hedonic (e bonts'a thabo), empa pono ena e belaelletsoe ke pharmacological blockade, lesion (48), le lithuto tsa lefutso (49) moo liphoofolo li tsoetseng pele ho khetha ("joalo") meputso e joalo ka sucrose leha ho felisitsoe ke dopamine. Ho feta moo, liketso tsa nicotine esale e le sephiri tlalehong ena, hobane nicotine e lemalla haholo 'me e baka tokollo ea dopamine empa e hlahisa nyakallo e nyane haholo.

Sebakeng sa ho sebetsa joalo ka sesupo sa hedonic, dopamine e bonahala e khothaletsa thuto e amanang le moputso, e tlama likarolo tsa hedonic tsa sepheo sa ho lakatsa le ho nka khato, ka tsela eo li bopa boitšoaro bo amanang le moputso bo latelang (48). Lenaneong la bohlokoa la liteko tse kenyeletsang lirekoto tse tsoang ho litšoene tse lemosang, Schultz le basebetsi mmoho (8, 50-52) e batlisisitse maemo ao ho ona mollo oa "midbrain dopamine neurons fire" o amanang le moputso. Liteko tsena li fane ka leseli la bohlokoa ka kakaretso mabapi le tlhahiso ea dopamine empa eseng ka diketso tse fapaneng tsa dopamine ho li-nucleus accumbens, dorsal striatum, amygdala, le preortalal cortex. Schultz et al. a rekota ho tsoa ho dopamine neurons ha litšoene li ne li lebelletse kapa li ja lero le monate, e le tšusumetso e ntle. Litšoene li ile tsa koetlisetsoa ho lebella lero ka mor'a nako e tsitsitseng kamora ho bona kapa ho bua. Se hlahileng e ne e le mokhoa o fetohileng oa ho thunya ha methapo ea dopamine ha litšoene li ithuta maemo ao meputso e bang teng ka tlasa ona. Ho litšoene tse tsohileng, dopamine neurons e bontša mokhoa oa ho thunya o sa fetoheng (tonic) o sa fetoheng; tse bonoang ka mokhoa ona oa motheo ke liketsahalo tse khutšoanyane tsa ts'ebetso ea spike, nako ea eona e khetholloang ke boiphihlelo ba pele ba phoofolo ka meputso. Ka ho khetheha, moputso o sa lebelloang (ho tsamaisoa ha lero) o hlahisa keketseho ea nakoana ea ho thunya, empa ha tšoene e ithuta hore matšoao a itseng (molumo kapa leseli) a bolela moputso ona, nako ea ketsahalo ena ea phasic e fetoha. Li-neuropropa tsa dopamine ha li sa bonts'a ho phatloha ha phasic ha ho etsoa lero, empa li etsa joalo pejana, ka lebaka la ts'usumetso e boletsoeng esale pele. Haeba ts'usumetso e hlahisoa eo hangata e amanang le moputso empa moputso o thibetsoe, ho na le khefu ho turu ea tonic ea dopamine ka nako eo moputso o neng o ka lebelloa. Ka lehlakoreng le leng, haeba moputso o tla ka nako e sa lebelloang kapa o lebelletse tebello e fetisisang, phasic e phatloha ka ho thunya e bonoa. Ho 'nile ha nahanoa hore lits'oants'o tsena tsa phasic le likhefutso li ts'oara pontšo ea phoso. Ts'ebetso ea tonic ha e supe ho kheloha ho lebella, empa phasic e phatloha e bonts'a phoso e boletsoeng esale pele ea moputso (e betere ho feta kamoo e neng e lebelletsoe), e ipapisitseng le nalane e akaretsang ea phumants'o ea meputso, mme e emisa ho bonts'a phoso e mpe ea bolepi (9, 53). Leha e lumellana le liphuputso tse ling tse ngata, liphuputso tsa liteko tsena tse boima ha li so ka li etsoa ka botlalo lilaboratoring tse ling ebile ha li so etsetsoe meputso ea lithethefatsi; ka hona, ts'ebeliso ea bona ea lithethefatsi tse lemalloang e ntse e le boima. Ho bohlokoa ho hlokomela hore mosebetsi ona o ka bolela monyetla o mong oa tlatsetso bakeng sa lithethefatsi ho feta meputso ea tlhaho. Ka lebaka la liketso tsa bona tse tobileng tsa litlhare, bokhoni ba bona ba ho eketsa maemo a dopamine ts'ebetsong bo ke ke ba senyeha ha nako e ntse e ea. Kahoo, boko bo ne bo tla fumana pontšo ea hore lithethefatsi li "betere ho feta kamoo ho neng ho lebelletsoe" kateng.

Berridge le Robinson (48) e bontšitse hore dopamine ha e hlokehe bakeng sa thepa e khahlisang (hedonic) ea sucrose, eo, lipatlisisong tsa bona, e tsoetseng pele ho "ratoa" ke likhoto tse felisitsoeng ke dopamine. Sebakeng seo ba hlahisitse hore nucleus accumbens dopamine transmission e fana ka kabelo ea "incentive salience" ho putsa le ho amana le meputso, joalo ka hore lintlha tsena li ka baka boemo ba "ho batla" sepheo sa sepheo se fapaneng le "ho rata". Ho ea ka bona, phoofolo e ntse e ka "rata" ho hong ha ho se na phetiso ea dopamine, empa phoofolo e ke ke ea sebelisa leseli lena ho susumetsa boits'oaro bo hlokahalang ho e fumana. Ka kakaretso, ho ka fihlela qeto ea hore tokollo ea dopamine ha se setšoantšo sa kahare sa thepa ea hedonic ea ntho; liteko tsa Schultz et al. fana ka maikutlo a hore dopamine e sebetsa e le lets'oao la phoso ea ho bolela esale pele le bopehang boits'oarong ho fumana meputso ka nepo.

Pono ena ea ts'ebetso ea dopamine e lumellana le mehlala e rarahaneng ea ho ithuta ho matlafatsa (9, 53, 54). Meetso e matlafatsang ea ho ithuta e ipapisitse le khopolo-taba ea hore sepheo sa sebopuoa ke ho ithuta ho sebetsa ka tsela e tla eketsa meputso ea kamoso. Ha mefuta e joalo e sebelisoa boitsebisong ba 'mele bo hlalositsoeng pejana, ho khefutsa le ho ts'oaroa hoa phasic ea li-dopamine neurons ho ka nahanoa e le setšoantšo sa kahare sa liphoso tsa ho bolela esale pele ka moputso oo liketso tsa monkey ("moemeli") tse reriloeng kapa tsa nnete li "nyatsoang" ke tsona matšoao a matlafatso (ke hore, meputso e qetellang e le betere, e mpe le ho feta kapa ho latela kamoo ho boletsoeng esale pele). Ho lokolloa ha Dopamine ho ka etsa hore ho rutoe-ho putsa ho ithuta ho ntlafatsa ho bolela esale pele ha ho ntse ho bopa boithuto ba ketso ea bohato, ke hore, karabelo ea boits'oaro ho susumetso e amanang le moputso. (8, 9). Ka lebaka la monyetla oa hore lithethefatsi tse lemalloang li feta ts'usumetso ea tlhaho ts'epelong, bongata, le phehelong ea litekanyetso tsa dopamine tse eketsehang, sephetho se boletsoeng esale pele sa litekanyetso tsena e ka ba tlatsetso e kholo ea bohlokoa bo susumetsang ba litheko tse bolelang esale pele ho tlisoa ha lithethefatsi. Ka nako e ts'oanang, ho hongata ho lula ho sa hlakileng. Mohlala, litšoeneng tse ithutoang ke Schultz le basebetsi mmoho, ho phatloha hanyane le hanyane ho thunya ha dopamine neuron ho sebetsa e le pontsho ea phoso. Leha ho le joalo, lithethefatsi tse kang amphetamine li ka sebetsa lihora tse ngata mme ka hona, li ka senya mekhoa eohle e tloaelehileng ea tokollo ea dopamine, tonic le phasic, ho hlahisa lets'oao le sa tloaelehang la dopamine. Litlamorao tsa dopamine kinetics tse amanang le lithethefatsi mabapi le boitšoaro bo amanang le moputso li se li qalile ho ithutoa (55).

Karolo ea Cortex ea Pele

Tlas'a maemo a tloaelehileng, libopuoa li nka lipheo tse ngata, li etsa hore ho hlokehe hore li khethoe har'a tsona. Karolo ea bohlokoa ea bokhoba ba tahi ke ho fokotseha hoa khetho ea sepheo ho ba amanang le lithethefatsi. Seemeli sa lipheo, kabelo ea boleng ho bona, le khetho ea liketso ho latela boleng bo hlahisitsoeng bo ipapisitse le cortex ea pele. (56-59). Ho phethela ka katleho mokhoa o tataisoang ke sepheo, ebang ke oa ho theola (kapa mehleng ea kajeno, mabenkeleng) bakeng sa lijo kapa ho batlana le heroin, ho hloka tatellano e thata le e atolositsoeng ea liketso tse lokelang ho ts'oaroa ntle le litšitiso le litšitiso. Taolo ea kelello e lumellang boitšoaro bo tataisoang ke sepheo ho fihlela sephetho se atlehileng ho nahanoa hore e latela ts'ebetso ea ts'ebetso ea maano a sepheo kahara kotara ea pele. (56, 59). Ho ea pele, ho nahanoa hore matla a ho ntlafatsa tlhahisoleseling kahare ho cortex ea pele e le hore merero e mecha e ka khethoa le mamello e qojoe e fanoa ke phasic dopamine release (8, 60).

Haeba phasic dopamine e lokolla e fana ka lets'oao la gating ka pele ho cortex, lithethefatsi tse tlatsetsang li ka hlahisa sesupo se matla empa se sothehileng se sitisang thuto e tloaelehileng e amanang le dopamine ho cortex ea pele, hammoho le ka har'a li-nucleus accumbens le dorsal striatum. (9, 19). Ho feta moo, ho motho ea lemalloang, tloaelo ea tlhaho ea ho pheta-pheta, phetoho e ngata haholo ea dopaminergic (61) e ka fokotsa likarabo tsa meputso ea tlhaho kapa litheko tse amanang le moputso tse eketsang tshusumetso ea dopamine, ha li bapisoa le lithethefatsi tse bakang ka kotlolloho dopamine; ka mantsoe a mang, tšusumetso ea tlholeho e kanna ea hloleha ho bula mochine o kopantsoeng oa ho itšepa pele ho motho ea lemalloang, ka hona a hloleha ho susumetsa khetho ea sepheo. Keketseho ea boemo bo joalo e ka ba sesupo sa lefats'e, le matla ho feta tekano lithahasellong tse amanang le lithethefatsi le hole le liqeto tse ling, ka hona, tlatsetsa tahlehelong ea taolo ea ts'ebeliso ea lithethefatsi eo e leng tšobotsi ea ho lemalla. Hoa thahasellisa ho hlokomela hore lithuto tsa pele tsa neuroimaging li tlaleha mokhoa o sa tloaelehang oa ts'ebetso ea cingex cortex le orbital pele ho cortex lithutong tse lemaletseng. (62-64).

Le ha ho hlokahala lipatlisiso tsa methapo e mengata ho utloisisa litlamorao tsa lipontšo tsa dopamine tsa tonic le phasic, mekhoa eo lithethefatsi tse lemalloang li ba sitisang ka eona, le litlamorao tse sebetsang tsa pherekano eo, kutloisiso ea karolo ea dopamine lithutong tse peli tse khothatsang tsa moputso le khothatso. - Ho ithuta ka taba ho na le litlamorao tse ngata tsa bohlokoa tlhahisong ea bokhoba ba lithethefatsi. Lits'oaetso tse bolelang esale pele hore ho ka fumaneha lithethefatsi li ka nka sesosa se matla sa ts'ebetso, ka liketso tsa dopamine ho li-bokellase tsa nucleus le cortex ea pele, le litekanyetso tsa boits'oaro tse batlang lithethefatsi li ka matlafatsoa ka matla ke liketso tsa dopamine ka cortex ea pele le dorsal striatum. (9, 18, 19, 23, 65).

Stimulus-moputso le stimulus-action ithuta li amahanya lintlha tse ikhethileng, tse etsahalang maemong a itseng, ka litlamorao tse kang "ho batla" moputso, ho nka bohato ba ho fumana moputso, le ts'ebeliso ea moputso. (Karolo ea bohlokoa ea moelelo ke hore na tlhahiso e fanoa haufi le moputso [66]; mohlala, ho ba le chate e amanang le lithethefatsi ka laboratoring ho na le moelelo o fapaneng bakeng sa ts'ebetso ho fapana le ho bona seterata se tšoanang le seterateng.) Ho ithuta bohlokoa ba cue le ho hokahanya tlhahisoleseling le karabelo e nepahetseng ho hloka polokelo ea lintlha tse itseng bokong. Tlhahisoleseling ena e bolokiloeng e tlameha ho fana ka lipontšo tsa kahare tsa khothalletso e amanang le moputso, boleng ba eona, le tatellano ea tatellano ea liketso e le hore cue e ka baka karabelo e sebetsang le e sebetsang ea boits'oaro. (19). Ho lokela ho ba joalo le ka lithaba tse khelohelang tse bontšang kotsi.

Haeba mohopolo oa phoso ea ponelo-pele ea ts'ebetso ea dopamine o nepahetse, dopamine ea phasic e hlokahala bakeng sa boko ho ntlafatsa bohlokoa ba ponelo-pele ea cices. Haeba ts'ebetso ea dopamine-gating hypothesis ea preortal cortex e sebetsa hantle, phasic dopamine e hlokahala ho ntlafatsa khetho ea sepheo. Maemong ana ka bobeli, leha ho le joalo, dopamine e fana ka tlhaiso-leseling e akaretsang ka boemo bo susumetsang ba setho; dopamine neurons ha e qaqise leseli le qaqileng mabapi le meelelo, merero kapa liketso tse amanang le moputso. Moralo oa sistimi ea dopamine — palo e fokolang ea 'mele ea lisele e ka' nang ea hlaha hammoho 'me ea kenella hohle ka phatleng, ka methapo e le' ngoe e kenyang merero e mengata-ha e sebetse poloko ea tlhaiso-leseling e nepahetseng. (67). Sebakeng sena, moetso oa "o ts'oanang le spray" o loketse ho hokahanya likarabo ho tsa bohlokoa ho potoloha lipotoloho tse ngata tsa boko tse tšehetsang lipontšo tse nepahetseng tsa tlhaiso-leseling ea kutlo kapa tatellano ea liketso. Tlhahisoleseling e nepahetseng mabapi le ts'usumetso le seo e se bolelang esale pele (mohlala, hore alley e itseng, moetlo o itseng, kapa monko o itseng-empa eseng monko o amanang haufi-ufi - o noha phumants'o ea lithethefatsi) e ipapisitse le litsamaiso tsa kutlo le tsa memori tse rekotang lintlha tsa boiphihlelo ka botshepehi bo phahameng. Tlhahisoleseling e ikhethang mabapi le lintlha, tlhahlobo ea bohlokoa ba tsona, le likarabo tsa likoloi tse ithutoang li its'etleha ho lipotoloho tse tšehetsang phetisetso ea methapo ea kutlo le ho sebelisa li-neurotransmitter tse nyarosang tse kang glutamate. Kahoo, ke tšebelisano e kopaneng lipakeng tsa glutamate le dopamine neurons ka likarolo tse sebetsang tse fapaneng joalo ka li-nucleus accumbens, prefrontal cortex, amygdala le dorsal striatum (68, 69) e kopanyang lintlha tse ikhethileng tsa maikutlo kapa tatellano e ikhethang ea ketso le tsebo ka boemo ba tšusumetso ea setho le boiketlo ba likhakanyo tikolohong. Litlhokahalo tse sebetsang tsa ho hatisa tlhaiso-leseling e qaqileng mabapi le tšusumetso e amanang le moputso le karabelo ea ts'ebetso li kanna tsa tšoana le tse tlasa mefuta e meng ea memori ea nako e telele, ho tloha moo e latelang ka kotloloho mohopolo o lemalloang oa ts'ebeliso ea lits'oaetso tsa memori tse amanang le moputso. (11, 19).

Robinson le Berridge (30, 70) e hlahisitse pono e 'ngoe — tlhotlheletso e khothalletsang takatso ea ho lemalla. Ka maikutlo ana, tsamaiso ea lithethefatsi ea letsatsi le leng le le leng e hlahisa mamello ho litlamorao tse itseng tsa lithethefatsi empa ntlafatso e tsoelang pele — kapa e susumetsang — ea ba bang (71). Mohlala, ho litoeba, ho kenngoa ka mehla cocaine kapa amphetamine ea letsatsi le letsatsi ho hlahisa keketseho e tsoelang pele ea mosebetsi oa locomotor. Sensitization ke mohlala o khahlehang oa ho lemalla hobane ts'ebetso ea maikutlo ke mohopolo oa nako e telele le hobane mefuta e meng ea maikutlo e ka hlahisoa ka mokhoa o itšetlehileng ka maemo (72). Ka mohlala, haeba likhoto li fumana ente ea amphetamine letsatsi le leng le le leng ka hokong ea liteko ho fapana le matlo a bona a lapeng, li bonts'a boits'oaro bo matlafatsang ha li beoa hape ka hokong ea liteko. Khopolo ea khothatso ea maikutlo e fana ka maikutlo a hore joalo ka ha boits'oaro ba locomotor bo ka khothatsoa, ​​tsamaiso ea lithethefatsi e phetoang e matlafatsa sistimi ea methapo e fanang ka boits'oaro (ho fapana le boleng ba hedonic kapa "ho rata") ho lithethefatsi le litlamorao tse amanang le lithethefatsi. Boikhohomoso bona bo ka lebisa ho "ho batla" ho matla ha lithethefatsi tse ka sebelisoang ke litlhahiso tse amanang le lithethefatsi (30, 70). Ka kakaretso, pono ea ts'usumetso ea ts'usumetso e lumellana le maikutlo a hore dopamine e sebetsa e le lets'oao la tlhatlhobo la moputso (9). Ho ka boela ha bonahala e le taba e sa utloahaleng hore menyetla ea litšusumetso tse amanang le lithethefatsi e ntlafatsoa ho batho ba lemaletseng lithethefatsi. Ho feta moo, ha ho na khohlano ea hore bokhoni ba mekhoa ena ea ho kenya ts'ebetsong takatso ea lithethefatsi kapa ho tsoma lithethefatsi ho latela mekhoa e amanang le ho ithuta. Taba ea ho se lumellane ke hore na mokhoa oa neural oa sensitization, joalo ka ha o utloisisoa hona joale ho tsoa mehlaleng ea liphoofolo, o bapala karolo e hlokahalang tlatsong ea batho. Mehlaleng ea liphoofolo, boitšoaro ba sensomotor bo hlophisitsoeng bo qalisoa sebakeng sa karohano ea mocheso ebe bo hlahisoa ka har'a li-nucleus accumbens (73, 74), mohlomong ka ntlafatso ea likarabo tsa dopamine. Ha ho fanoa ka homogeneity e lekanang ea likhakanyo tsa sebaka sa karolelano ea methapo ea kutlo sebakeng se bokellaneng kapa ho cortex ea pele le bokhoni ba likhakanyo tsena tsa ho sebelisana le li-neurons tse ngata, ho thata ho hlalosa hore na karabelo ea dopamine e ntlafalitsoeng e ka kopantsoe joang le lithethefatsi tse itseng- mekhoa e amanang le eona ntle le ho bitsa mekhoa ea memori e amanang. Leha ho na le lingoliloeng tse ntseng li ferekantsoe tsa liteko, bopaki ba morao-rao bo tsoang phuputsong ea litoeba tsa gene-knockout tse se nang tšebetso ea AMPA glutamate receptors bo fumane ho se utloane pakeng tsa sensitization ea cocaine e kenyellelitsoeng ho cocaine (e neng e bolokiloe mokhoeng oa ho kobeha) le thuto e kopaneng; ka mantsoe a mang, litoeba ha li sa bonts'a karabelo ea boemo ba sebaka ha e ne e beoa taba e neng e amana le cocaine, hape ha ea ka ea bontša ho rata libaka. (75). Bonyane liteko tsena li hatisa karolo ea bohlokoa ea mekhoa e amanang ea ho ithuta bakeng sa ho kenyeletsa itseng litekanyetso tsa lithethefatsi le bakeng sa ho hokahanya likhoele tsena le itseng likarabo (19, 23). Le ha maikutlo a ne a ka bonts'oa bathong (a e-so ka a etsoa ka mokhoa o kholisang), ha ho tsejoe hore na karolo ea bona e ka ba eng ho feta ho ntlafatsa mekhoa ea ho ithuta e itšetlehileng ka dopamine ka ho eketsa tlhahiso ea dopamine maemong a ikhethang. Ke litsamaiso tsa ho ithuta tse ikarabellang bakeng sa ho kenyelletsa moemeli oa litheko tse sa tloaelehang tsa lithethefatsi le ho li hokahanya le boits'oaro bo itseng bo batlang lithethefatsi le karabelo ea maikutlo.

Qetellong, tlhaloso ea bokhoba ba tahi e hloka mohopolo oa ho phehella ha eona. Ho na le lipotso tse ngata tse mabapi le mekhoa eo mehopolo ea nako e telele e tsoelang pele lilemo tse ngata kapa bophelo bohle (15, 16, 76). Ho tloha ntlheng ena ea maikutlo, likarabo tsa dopamine tse khahlisang lithethefatsi le litheko tsa lithethefatsi li ka lebisa ho kopaneng e matlafalitsoeng ea mehopolo e amanang le lithethefatsi, empa ho phehella ho tšebeliso ea lithethefatsi ho ka utloahala ho ipapisitse le ntlafatso ea li-synapses le li-circuits tseo ho nahanoang hore ke tšobotsi ea memori ea nako e telele e amanang (15, 16).

Joalokaha ho bontšitsoe ke puisano e boletsoeng ka holimo, mekhahlelo ea limolek'hule le lisele tsa boits'oaro maemong a boits'oaro le litsamaiso qetellong li tlameha ho hlalosa 1) hore na liketsahalo tse phetoang khafetsa tsa tokollo ea dopamine li kopanya boits'oaro ba tšebeliso ea lithethefatsi ts'ebelisong e qobelloang, Naha e lokolohileng e ka phehella lilemo, le 2) hore na litloaelo tse amanang le lithethefatsi li laola boitšoaro joang. Mekhoa ea ho saena kahare ho sele e hlahisang polasetiki ea synaptic ke mekhoa e metle ea likhetho bakeng sa ho lemalla hobane e ka fetola matšoao a susumetsoang ke lithethefatsi, joalo ka tokollo ea dopamine, hore e be liphetoho tsa nako e telele ts'ebetsong ea methapo mme qetellong e be ntlafatso ea lipotoloho tsa neuronal. Polasetiki ea Synaptic e rarahane, empa e ka aroloa ka mokhoa oa heuristic ka mekhoa e fetolang matla kapa "boima" ba likhokahano tse teng le tse ka lebisang ho sebopeho sa synapse kapa ho felisa le ho nchafatsa sebopeho sa dendrites kapa axon. (15).

Joalokaha ho hlalositsoe, bohlokoa ba litekanyetso tsa lithethefatsi le kamano ea tsona ho tatellano e itseng ea boits'oaro e fana ka maikutlo a hore bonyane mekhoa e meng e tlatselletsang bokhobeng ba tlhekefetso e tlameha ho ba e amanang le ho hasana ho khethehileng. Mekhoa e khethiloeng ka ho fetisisa ea mokhethoa oa ho fetola matla a synaptic a amanang ka bobeli le a kopaneng a rarahaneng ke tšusumetso ea nako e telele le khatello ea maikutlo ea nako e telele. Mechine ena e kentse letsoho ho bapala likarolo tsa bohlokoa mefuteng e mengata ea boits'oaro bo ts'epahallang boiphihlelo, ho kenyelletsa mefuta e fapaneng ea ho ithuta le ho hopola (77, 78). Methati e joalo ea polasetiki ea synaptic e ka lebisa kamora ho hlophisoa bocha ha neural circry ka ho fetola mofuta oa polelo le polelo ea liprotheine ho li-neurons tse amohelang matšoao a ntlafalitsoeng kapa a fokotsehileng ka lebaka la tšenyo ea nako e telele kapa khatello ea maikutlo ea nako e telele. Monyetla oa nako e telele le khatello ea maikutlo ea nako e telele joale e fetohile mekhoa ea bohlokoa ea mokhethoa bakeng sa liphetoho tse tlisoang ke lithethefatsi tsa ts'ebetso ea potoloho ea neural e ikemiselitseng ho etsahala ka bokhoba ba tahi. (11). Hona joale ho na le bopaki bo botle ba hore mekhoa ena ka bobeli e etsahala ka har'a li-nucleus accumbens le sepheo se seng sa mesolimbic dopamine neurons ka lebaka la taolo ea lithethefatsi, mme bopaki bo ntseng bo hola bo fana ka maikutlo a hore li ka bapala karolo ea bohlokoa ntlafatsong ea bokhoba ba tahi. Puisano e qaqileng ea liphetho tsena e feta tekano ea tlhahlobo ena (bakeng sa litlhahlobo, bona litšupiso 11, 79-81). Mechine ea limolek'hule e tlasa ts'ebetso ea nako e telele le khatello ea maikutlo ea nako e telele e kenyelletsa ho laola boemo ba phosphorylation ea liprotheine tsa bohlokoa, liphetoho lipakeng tsa li-receptor tsa glutamate sebakeng sa synapse, le taolo ea polelo ea gene (78, 82).

Potso ea hore na mehopolo e lula e phehella joang (15, 16, 76) e sebetsa haholo ho bokhoba ba tahi mme ha e-so arabe ka mokhoa o khotsofatsang, empa ho phehella ho nahanoa hore ho kenyelletsa ho hlophisoa bocha ha li-synapses le li-circuits. Liphetho tsa pele tse nyarosang li bonts'itse hore amphetamine le cocaine li ka hlahisa liphetoho tsa morphological ho dendrites kahare ho li-nucleus accumbens le cortex ea pele. (83, 84).

Mochine oa bohlokoa oa mokhethoa oa ho nchafatsa 'mele oa li-dendrites, axons le li-synapses ke phetoho e tlisoang ke lithethefatsi ho polelo ea gene kapa phetolelong ea protheine. Nakong e feteletseng ea nako, mefuta e 'meli ea taolo ea liphatsa tsa lefutso e ka kenya letsoho mohopolong oa nako e telele, ho kenyelletsa le methapo ea memori ea methapo e boletsoeng: 1) e phetse nako e telele-kapa tlase-taolo ea polelo ea mofuta kapa liprotheine le 2 ) ho phatloha ho bokhutšoanyane ha polelo ea gene (kapa phetolelo ea protheine) e lebisang ntlafatsong ea 'mele ea li-synapses (ke hore, liphetoho tsa morphological tse lebisang phetohong ea matla a synaptic, molumo oa li-synapses tse ncha, kapa ho roka ha li-synapses tse teng) mme, ka hona, ho hlophisetsanoeng ha liserekisi. Mefuta ka bobeli ea liphetoho lipuong tsa gene e se e bonoa ho arabela ho ts'oaroa ha dopamine le lithethefatsi tse lemalloang tse kang koae (85, 86).

Phetoho ea molek'hule e phetseng nako e telele haholo eo hona joale e tsejoang e etsahala ka lebaka la lithethefatsi tse lemalloang (le tse ling tse susumetsang) ho li-nucleus tsa li-nucleus le dorsal striatum ke molao-motheo oa mekhoa e tsitsitseng ea posttranslationally e fetotsoeng ea transcript factor ΔFosB (85). Qetellong e 'ngoe ea sebata sa nakoana ke polelo ea nakoana (metsotso ho isa ho lihora) ea palo e kholo ea liphatsa tsa lefutso e ka itšetlehang ka ts'ebetso ea dopamine D1 li-receptors le of transaction factor CREB, protheine ea cyclic ea AMP ea cyclic e tlamang (86). CREB e hlahisoa ke li-kinases tse ngata tsa liprotheine, ho kenyelletsa le cystlic e itšetlehileng ka protheine ea AMP le liC tse 'maloa2+-notein protein tse itšetlehileng ka mofuta oa calcium oa mofuta oa IV oa "proteinodase" (87, 88). Hobane CREB e ka arabela ka bobeli cyclic AMP le Ca2+ tsela 'me ka hona e ka sebetsa joalo ka ha e kopantsoe ke tsietsi, ts'ebetso ea eona e bonoe e le mokhethoa oa ho nka karolo ho matlafatsong ea nako e telele le mohopolong o kopaneng. Ebile, sehlopha se seholo sa lipatlisiso ka bobeli li-invertebrates le litoeba li tšehetsa karolo ea bohlokoa bakeng sa CREB mohopolong oa nako e telele (bakeng sa litlhahlobo, bona litšupiso 87 'me 88).

Ha re fuoa mohopolo oa ho lemalla e le tšebeliso ea kelello ea nako e telele, re fuoa karolo e tsitsitseng ea CREB ka mefuta e mengata ea mohopolo oa nako e telele. (87, 88), le ho fuoa bokhoni ba koae le cofine tse sebetsang (88-90), ho bile le thahasello e kholo mabapi le karolo e ka khonehang ea CREB ho kopantseng mehopolo e amanang le moputso (11, 19). Bopaki bo tobileng ba karolo e joalo bo ntse bo haella. Leha ho le joalo ho na le bopaki bo matla bo hokahanyang cocaine le amphetamine e susumetsang ea dopamine D1 receptor-CREB tsela ea ho mamella le ho its'etleha. Mofuta oa "CREB" o hlophisitsoeng hantle o ithutoang hantle o ka bang le mamello le ts'ehetso ke mofuta oa prodynorphin (91-93), e emisang li-peptide tsa endio native opioid dynorphin tse leng kappa opioid receptor agonists. Cocaine kapa amphetamine e lebisa ho dopamine ho hlohlona ha D1 receptors ka li-neuron bokong bokellane le dorsal striatum, e lebisang ho CERB phosphorylation le activation of prodynorphin gene expression (93). Li-peptide tse hlahisang dynorphin li isoa li-axon tse kopaneng tsa methapo ea kutlo, eo ka eona li thibelang ho lokolloa ha dopamine litsing tsa methapo ea methapo ea methapo ea methapo, kahoo li fokotsa karabelo ea lits'ebetso tsa dopamine. (91, 94). D1 keketseho ea lipakeng ea receptor ka har'a dynorphin e ka nkoa e le mokhoa o ikhethileng oa homeopatic le ho tsosa dopamine ka mokhoa o feteletseng oa li-neurons tse mabapi le li-nucleus tsa li-nucleus le li-drial striatum tse iphelisang bakeng sa ho omella tokollo ea dopamine hape. (91). Tumellanong le mohopolo ona, ho feta ha CREB bokong bo bokellanang ka sethala sa vaerase ho eketsa polelo ea mofuta oa prodynorphin mme ho fokotsa litlamorao tse khahlisang tsa koae (95). Liphetho tse thabisang tsa koae li ka khutlisoa ka mokhoa ona ka tsamaiso ea mohanyetsi oa kappa receptor (95).

Litloaelo tsa homeostatic tse kang ho kenngoa ha dynorphin, e fokotsang karabelo ea lits'ebetso tsa dopamine, li ka bonahala li bapala karolo ho itšetleheng le ho tloseng. (26, 96). Fuoa karolo e lekanyelitsoeng ea ho itšepa ho pathogene ea ho lemalla (6, 11, 19, 27, 40), lithuto tse ling li tsepamisitse maikutlo mokhoeng o ka 'nang oa kenya letsoho ho ntlafatseng moputso oa lithethefatsi (bakeng sa litlhahlobo, bona litšupiso 12, 13). Moemeli ea ithutileng hantle ho fihlela joale ke sengoloa sa trans ΔFosB. Ho fetella ka nako e telele bakeng sa ΔFosB ka mokhoa o sa sebetseng oa panya ea transgenic ho okelitse litholoana tse monate tsa koae, 'me khatello e matla ea CREB le polelo ea nakoana ea ΔFosB e bile le litlamorao tse fapaneng tsa ho fokotsa moputso oa lithethefatsi (97). Ntle le moo, boemo bo fapaneng bo hlakileng ba polelo ea sebini bokong ba mouse bo hlahisitsoe ke polelo ea nako e telele ea ΔFosB, ha e bapisoa le CREB kapa polelo ea nakoana ea ΔFosB (97). Litlamorao tsa liphumano tsena ke hore bonyane mefuta e meng e hlahisitsoeng ka tlase ho CREB, joalo ka mofuta oa pro-dynorphin (93), ba nka karolo ho mamellaneng le ho tšepahallong le hore mefuta ea tlhaho e hlalositsoeng tlase ΔFosB e kanna ea ba likhetho bakeng sa ho ntlafatsa likarabo ho meputso le ho fumana meputso e amanang le moputso. Tlhahlobo e thatafatsoa ke mahlale a liteko a teng hobane mekhoa eohle ea ho ikatisa ka mokhoa o feteletseng oa CREB e feta hantle nako e tloaelehileng ea metsotso (metsotso) ea phosphorylation ea CREB le dephosphorylation tlasa maemo a tloaelehileng. Kahoo, karolo ea CREB ho kopanya likhopotso tse amanang le moputso ha ea lokela ho lahloa motheong oa bopaki bo teng. Boiteko bo bocha ba ho ntlafatsa mefuta ea liphoofolo tse lemalloang (98, 99) e ka ba molemo haholo boitekong ba ho hokahanya polelo e sa sebetseng ea mofuta oa lithethefatsi le polasetiki ea synaptic, ho nchafatsoa hoa kutlo le boitšoaro bo nepahetseng.

The dopamine hypothesis ea ts'ebetso ea lithethefatsi e fumane chelete e tlase ho lilemo tse mashome a mabeli tse fetileng (38-40). Ka nako eo, dopamine e ne e kholoa e le lets'oao la hedonic, 'me temallo e ne e utloisisoa haholo ka mantsoe a hedonic, ka ho ts'epahalla le ho tlohela ho ne ho nkoa e le mokhanni oa bohlokoa oa ho sebelisa lithethefatsi hampe. Boiteko ba morao-rao bo boholo maemong a fapaneng a tlhahlobo bo fane ka setšoantšo se matla le se rarahaneng haholo sa ketso ea dopamine le hore na e ka hlahisa temallo joang, empa tlhaiso-leseling e ncha le liqapi tse ncha tsa thuto li hlahisitse lipotso tse ngata kamoo li arabileng. Thutong ena ke re taba ea hore seo re se tsebang ka bokhoba ba letsatsi la kajeno se molemo ka ho fetisisa ke maikutlo a hore e emela ts'ebetso ea methapo ea ho ithuta le ho hopola lintho tse amanang le moputso. Leha ho le joalo, ho tlameha hape ho hlakeloe hore likotoana tse ngata tsa puzzle ha li na letho, ho kenyelletsa le tse ling tse kholo joalo ka mokhoa o nepahetseng moo lithethefatsi tse fapaneng li sitisang tonic le phasic dopamine ho supa lipotolohong tse fapaneng, litlamorao tsa ts'itiso eo, le methapo ea methapo ea kutlo le limolek'hule tseo ka tsona lithethefatsi tse lemalloang li hopotsang liphokotso le lipotoloho. Liphephetso tsena ho sa tsotelehe, neuroscience ea mantlha le ea bongaka li hlahisitse setšoantšo se nepahetseng le se matla sa lemallo ho feta kamoo re neng re le lilemong tse 'maloa tse fetileng.

E amohetse Aug. 19, 2004; ntlafatso e amohetse Nov. 15, 2004; Dec. 3 e amohetseng, 2004. Ho tsoa Lefapheng la Neurobiology, Sekolo sa Bongaka sa Harvard, Boston; le Ofisi ea Provost, Univesithi ea Harvard. Ikopanye le mangolo le likopo tsa ho hatisa ho Dr. Hyman, Ofisi ea Provost, Hall ea Massachusetts, Univesithi ea Harvard, Cambridge, MA 02138; [imeile e sirelelitsoe] (imeile).

1
Hser YI, Hoffman V, Grella CE, Anglin MD: Ho latela lilemo tse 33 tsa batho ba lemaletseng lithethefatsi. Arch Gen Psychiatry 2001; 58: 503-508
[Lebokose]
[CrossRef]
2
McLellan AT, Lewis DC, O'Brien CP, Kleber HD: Ho itšetleha ka lithethefatsi, bokuli bo sa foleng ba bongaka: litlamorao tsa kalafo, inshorense le tlhahlobo ea sephetho. JAMA 2000; 284: 1689-1695
[Lebokose]
[CrossRef]
3
Merikangas KR, Stolar M, Stevens DE, Goulet J, Preisig MA, Fenton B, Zhang H, O'Malley SS, Rounsaville BJ: Phetiso e tloaelehileng ea mathata a ts'ebeliso ea lithethefatsi. Arch Gen Psychiatry 1998; 55: 973–979
[Lebokose]
[CrossRef]
4
Kendler KS, Prescott CA, Myers J, Neale MC: Sebopeho sa lisosa tsa liphatsa tsa lefutso le tikoloho bakeng sa mathata a tloaelehileng a kelello le ts'ebeliso ea lithethefatsi ho banna le basali. Arch Gen Psychiatry 2003; 60: 929-937
[Lebokose]
[CrossRef]
5
Rhee SH, Hewitt JK, Young SE, Corley RP, Crowley TJ, Stallings MC: Litšusumetso tsa lefutso le tikoloho ho keneng ha lithethefatsi, ts'ebeliso le ts'ebeliso ea mathata ho bacha. Arch Gen Psychiatry 2003; 60: 1256-1264
[Lebokose]
[CrossRef]
6
Wikler A, Pescor F: Boemo ba khale ba ketsahalo ea ho ithiba ea morphine, ho matlafatsa boits'oaro ba joala ba opioid le "ho khutlela morao" likhoto tse lemaletseng morphine. Psychopharmacologia 1967; 10: 255–284
[Lebokose]
[CrossRef]
7
O'Brien CP, Childress AR, Ehrman R, Robbins SJ: Lisosa tsa maemo a ts'ebeliso e mpe ea lithethefatsi: na li ka hlalosa ho qobelloa? J Psychopharmacol 1998; 12: 15–22
[Lebokose]
[CrossRef]
8
Schultz W, Dayan P, Montague PR: Karolo ea neural ea ho bolela esale pele le moputso. Saense 1997; 275: 1593–1599
[Lebokose]
[CrossRef]
9
Montague PR, Hyman SE, Cohen JD: Likarolo tsa likhomphutha bakeng sa taolo ea boitšoaro. Tlhaho 2004; 431: 760-767
[Lebokose]
[CrossRef]
10
Redish AD: Bokhoba joaloka ts'ebetso ea likhomphutha bo senyehile. Saense 2004; 306: 1944–1947
[Lebokose]
[CrossRef]
11
Hyman SE, Malenka RC: Bokhoba le boko: neurobiology ea qobello le ho phehella ha eona. Nat Rev Neurosci 2001; 2: 695-703
[Lebokose]
[CrossRef]
12
Nestler EJ: Likarolo tse tloaelehileng tsa limolek'hule le lisele tsa ho lemalla le ho hopola. Neurobiol Ithute Mem 2002; 78: 637-647
[Lebokose]
[CrossRef]
13
Chao J, Nestler EJ: Neurobiology ea limolek'hule ea bokhoba ba lithethefatsi. Annu Rev Med 2004; 55: 113–132
[Lebokose]
[CrossRef]
14
Kelley AE: Ho hopola le ho lemalla: li-neural circry tse arolelaneng le mekhoa ea limolek'hule. Neuron 2004; 44: 161-179
[Lebokose]
[CrossRef]
15
Chklovskii DB, Mel BW, Svoboda K: Cortical rewiring le polokelo ea tlhaiso-leseling. Tlhaho 2004; 431: 782-788
[Lebokose]
[CrossRef]
16
Dudai Y: Lits'ebeletso tsa limolek'hule tsa mehopolo ea nako e telele: potso ea ho phehella. Curr Opin Neurobiol 2002; 12: 211–216
[Lebokose]
[CrossRef]
17
White NM: Lithethefatsi tse lemalloang joalo ka lihokelo Bokhoba ba 1996; 91: 921–949
[Lebokose]
[CrossRef]
18
Robbins TW, Everitt BJ: Ho lemalla lithethefatsi: litloaelo tse mpe lia eketseha. Tlhaho 1999; 398: 567-570
[Lebokose]
[CrossRef]
19
Berke JD, Hyman SE: Bokhoba, dopamine, le limolek'hule tsa mohopolo. Neuron 2000; 25: 515-532
[Lebokose]
[CrossRef]
20
Robbins TW, Everitt BJ: Lits'ebetso tsa mohopolo oa Limbic-striatal le ho lemalla lithethefatsi. Neurobiol Ithute Mem 2002; 78: 625-636
[Lebokose]
[CrossRef]
21
Shizgal P, Hyman SE: Libaka tse khothatsang le tse lemalloang, ho Molao-motheo oa Neural Science, 5th ed. E hlophisitsoe ke Kandel ER, Schwartz JH, Jessell TM. New York, McGraw-Hill (ea khatiso)
22
Kelley AE, Berridge KC: Neuroscience ea meputso ea tlhaho: kamano ea lithethefatsi tse lemalloang. J Neurosci 2002; 22: 3306–3311
[Lebokose]
23
Berke JD: Mekhoa ea ho ithuta le ea ho hopola e amehang ts'ebelisong e mpe ea lithethefatsi le ho khutlela morao. Mekhoa Mol Med 2003; 79: 75-101
[Lebokose]
24
Hyman SE: Monna ea nang le joala le tšoaetso ea HIV. JAMA 1995; 274: 837-843
[Lebokose]
[CrossRef]
25
Hutcheson DM, Everitt BJ, Robbins TW, Dickinson A: Karolo ea ho tlohela ho lemalla heroin: e ntlafatsa moputso kapa e khothalletsa ho qoba? Nat Neurosci 2001; 4: 943–947
[Lebokose]
[CrossRef]
26
Koob GF, Le Moal M: Ts'ebeliso e mpe ea lithethefatsi: dysregulation ea hedonic homeostatic. Saense 1997; 278: 52-58
[Lebokose]
[CrossRef]
27
Stewart J, RA ea Bohlale: Ho khutlisetsoa ha litloaelo tsa boits'oaro ba heroine: litlamorao tsa morphine le naltrexone li nyahamisa ho arabela bocha kamora ho fela. Psychopharmacology (Berl) 1992; 108: 79-84
[Lebokose]
[CrossRef]
28
Marinelli M, Piazza PV: Tšebelisano lipakeng tsa lihormone tsa glucocorticoid, khatello ea maikutlo le lithethefatsi tsa psychostimulant. Eur J Neurosci 2002; 16: 387–394
[Lebokose]
[CrossRef]
29
Saal D, Dong Y, Bonci A, Malenka RC: Lithethefatsi tsa tlhekefetso le khatello ea maikutlo li baka tloaelo e tloaelehileng ea synaptic ho li-dopamine neurons. Neuron 2003; 37: 577-582; khalemelo, 38: 359
[Lebokose]
[CrossRef]
30
Robinson TE, Berridge KC: Bokhoba. Annu Rev Psychol 2003; 54: 25-53
[Lebokose]
[CrossRef]
31
Tiffany ST: Mohlala oa kutloisiso oa litabatabelo tsa lithethefatsi le boits'oaro ba ts'ebeliso ea lithethefatsi: karolo ea lits'ebetso tse iketsang le tse sa bonahaleng. Psychol Rev 1990; 97: 147-168
[Lebokose]
[CrossRef]
32
Tiffany ST, Carter BL: Na u lakatsa ho ba mohloli oa tšebeliso e mpe ea lithethefatsi? J Psychopharmacol 1998; 12: 23-30
[Lebokose]
[CrossRef]
33
Breiter HC, Gollub RL, Weisskoff RM, Kennedy DN, Makris N, Berke JD, Goodman JM, Kantor HL, Gastfriend DR, Riorden JP, Mathew RT, Rosen BR, Hyman SE: Litlamorao tse matla tsa cocaine ho ts'ebetso ea kelello ea motho le maikutlo. Neuron 1997; 19: 591-611
[Lebokose]
[CrossRef]
34
Vollm BA, de Araujo IE, Cowen PJ, Rolls ET, Kringelbach ML, Smith KA, Jezzard P, Heal RJ, Matthews PM: Methamphetamine e kenya tšebetsong meputso ea potoloho lithutong tsa batho ba se nang lithethefatsi. Neuropsychopharmacology 2004; 29: 1715-1722
[Lebokose]
[CrossRef]
35
Childress AR, Mozley PD, McElgin W, Fitzgerald J, Reivich M, O'Brien CP: Ts'ebetso ea Limbic nakong ea litakatso tsa cocaine tse hlohlelletsoang. Ke J Psychiatry 1999; 156: 11-18
[Lebokose]
36
CD ea Kilts, Schweitzer JB, Quinn CK, Gross RE, Faber TL, Muhammad F, Ely TD, Hoffman JM, Drexler KP: Ketsahalo ea Neural e amanang le takatso ea lithethefatsi lekhoba la cocaine. Arch Gen Psychiatry 2001; 58: 334-341
[Lebokose]
[CrossRef]
37
Bonson KR, Grant SJ, Contoreggi CS, Lihokela tsa JM, Metcalfe J, Weyl HL, Kurian V, Ernst M, London ED: Sistimi ea Neural le takatso ea coke e bakiloeng ke cueine. Neuropsychopharmacology 2002; 26: 376-386
[Lebokose]
[CrossRef]
38
RA ea bohlale, Bozarth MA: Khopolo-taba e susumetsang ea ho lemalla bokhoba ba kelello. Psychol Rev 1987; 94: 469–492
[Lebokose]
[CrossRef]
39
Di Chiara G: Khopolo-taba ea ho ithuta e susumetsang ea karolo ea mesolimbic dopamine ts'ebelisong e tlamang ea lithethefatsi. J Psychopharmacol 1998; 12: 54-67
[Lebokose]
[CrossRef]
40
Koob GF, Bloom FE: Mekhoa ea lisele le limolek'hule tsa ho itšetleha ka lithethefatsi. Saense 1988; 242: 715-723
[Lebokose]
[CrossRef]
41
Pontieri FE, Tanda G, Di Chiara G: K'hok'heine e kenang methapong, morphine le amphetamine ka ho khetheha li eketsa extracellular dopamine ho "khetla" ha e bapisoa le "mokokotlo" oa li-rat nucleus tsa rat. Proc Natl Acad Sci USA 1995; 92: 12304-12308
[Lebokose]
[CrossRef]
42
Everitt BJ, Parkinson JA, Olmstead MC, Arroyo M, Robledo P, Robbins TW: Mekhoa ea ho kopanya ho lemalla le ho putsa: karolo ea li-subsystem tsa amygdala-ventral striatal. Ann NY Acad Sci 1999; 877: 412-438
[Lebokose]
[CrossRef]
43
Johnson SW, North RA: Li-opioids li thabisa li-dopamine neurons ka ho fetelletsa litaba li-interneuron tsa lehae. J Neurosci 1992; 12: 483–488
[Lebokose]
44
Giros B, Jaber M, Jones SR, Wightman RM, Caron MG: Hyperlocomotion le ho se tsotelle k'hok'heine le amphetamine ho litoeba tse hlokang mopalami oa dopamine. Tlhaho 1996; 379: 606-612
[Lebokose]
[CrossRef]
45
Ventura R, Alcaro A, Puglisi-Allegra S: Ho ntšoa ha nortpinephrine ea pele ea cortical ho bohlokoa bakeng sa moputso o khothalletsoang oa morphine, ho khutlisetsoa le ho lokolloa ha dopamine ka har'a li-nucleus accumbens. Cereb Cortex 2005; Feb 23 epub
46
Montague PR, Berns GS: Moruo oa Neural le likarolo tsa biology tsa boleng. Neuron 2002; 36: 265–284
[Lebokose]
[CrossRef]
47
RA ea bohlale, Rompre PP: Brain dopamine le moputso. Annu Rev Psychol 1989; 40: 191-225
[Lebokose]
[CrossRef]
48
Berridge KC, Robinson TE: Karolo ea dopamine moputsong ke efe: tšusumetso ea hedonic, thuto ea moputso, kapa bohloeki bo khothatsang? Brain Res Boko Res Res 1998; 28: 309-369
[Lebokose]
49
Cannon CM, Palmiter RD: Moputso ntle le dopamine. J Neurosci 2003; 23: 10827-10831
[Lebokose]
50
Schultz W, Apicella P, Ljungberg T: Likarabo tsa monkey dopamine neurons ho putsa le ho ba le maemo nakong ea methati e latellanang ea ho ithuta mosebetsi o liehang oa ho arabela. J Neurosci 1993; 13: 900-913
[Lebokose]
51
Hollerman JR, Schultz W: Dopamine neurons e tlaleha phoso ponong ea nakoana ea moputso nakong ea ho ithuta. Nat Neurosci 1998; 1: 304-309
[Lebokose]
[CrossRef]
52
Schultz W: Pontšo ea moputso oa ponelopele ea li-dopamine neurons. J Neurophysiol 1998; 80: 1–27
[Lebokose]
53
Montague PR, Dayan P, Sejnowski TJ: Moralo oa litsamaiso tsa mesencephalic dopamine tse ipapisitseng le thuto ea se-Heberu e tlang pele. J Neurosci 1996; 16: 1936-1947
[Lebokose]
54
Sutton RS, Barto AG: Ho Ithuta ho Matlafatsa. Cambridge, Mass, MIT Press, 1998
55
Knutson B, Bjork JM, Fong GW, Hommer D, Mattay VS, Weinberger DR: Amphetamine e hlophisa ts'ebetso ea tšusumetso ea batho. Neuron 2004; 43: 261-269
[Lebokose]
[CrossRef]
56
Miller EK, Cohen JD: Khopolo-taba e kopanyang ea ts'ebetso ea preortal cortex. Annu Rev Neurosci 2001; 24: 167-202
[Lebokose]
[CrossRef]
57
Matsumoto K, Suzuki W, Tanaka K: Li-correlate tsa Neuronal tsa khetho ea makoloi e ipehetseng sepheo ho preortal cortex. Saense 2003; 301: 229-232
[Lebokose]
[CrossRef]
58
Roesch MR, Olson CR: Ketsahalo ea Neuronal e amanang le boleng ba moputso le otivation ho primate frontal cortex. Saense 2004; 304: 307-310
[Lebokose]
[CrossRef]
59
Rolls ET: Mesebetsi ea orbitofrontal cortex. Bokooa ba Bokooa 2004; 55: 11–29
[Lebokose]
[CrossRef]
60
Cohen JD, Braver TS, Brown JW: Menahano ea likhomphutha mabapi le ts'ebetso ea dopamine ho preortal cortex. Curr Opin Neurobiol 2002; 12: 223–229
[Lebokose]
[CrossRef]
61
Volkow ND, Fowler JS, Wang GJ, Hitzemann R, Logan J, Schlyer DJ, Dewey SL, Wolf AP: Ho fokotseha ha phallo ea receptor ea dopamine e amahanngoa le ho fokotsa metabolism e ka pele ho batho ba sebelisang hampe ba cocaine. Synapse 2; 1993: 14–169
[Lebokose]
[CrossRef]
62
Kaufman JN, Ross TJ, Stein EA, Garavan H. J Neurosci 2003; 23: 7839-7843
[Lebokose]
63
Volkow ND, Fowler JS: Bokhoba, lefu la ho qobelloa le ho khanna: ho nka karolo ha orbitofrontal cortex. Cereb Cortex 2000; 10: 318–325
[Lebokose]
[CrossRef]
64
Goldstein RZ, Volkow ND: Bokhoba ba lithethefatsi le motheo oa eona oa methapo ea kutlo: bopaki ba neuroimaging ba ho nka karolo ha cortex e ka pele. Ke J Psychiatry 2002; 159: 1642-1652
[Lebokose]
[CrossRef]
65
Graybiel AM: Basal ganglia le chunking ea liketso repertoires. Neurobiol Ithute Mem 1998; 70: 119–136
[Lebokose]
[CrossRef]
66
Shidara M, Richmond BJ: Anterior cingulate: matšoao a le mong a neuronal a amanang le tekanyo ea tebello ea moputso. Saense 2002; 296: 1709-1711
[Lebokose]
[CrossRef]
67
Foote SL, Morrison JH: Tlatsetso ea Extrathalamic ea ts'ebetso ea cortical. Annu Rev Neurosci 1987; 10: 67-95
[Lebokose]
[CrossRef]
68
McFarland K, Lapish CC, Kalivas PW: Prefrontal glutamate e lokolloa mokokotlong oa bokellane bo bokellanang bo khutlisetsang boits'oaro ba ts'ebeliso ea lithethefatsi. J Neurosci 2003; 23: 3531-3537
[Lebokose]
69
Kalivas PW: Sistimi ea Glutamate e lemaletseng koae. Curr Opin Pharmacol 2004; 4: 23–29
[Lebokose]
[CrossRef]
70
Robinson TE, Berridge KC: Motheo oa methapo ea takatso ea lithethefatsi: khopolo ea ts'usumetso ea ho lemalla bokhoba. Brain Res Boko Res Res 1993; 18: 247–291
[Lebokose]
71
Kalivas PW, Stewart J: Phetiso ea Dopamine ho qala le ho hlahisa ts'oaetso ea lithethefatsi le khatello ea maikutlo. Brain Res Boko Res Res 1991; 16: 223–244
[Lebokose]
72
Anagnostaras SG, Robinson TE: Sensitization ho litlamorao tse matlafatsang tsa psychomotor tsa amphetamine: modulation ka thuto e kopaneng. Behav Neurosci 1996; 110: 1397-1414
[Lebokose]
[CrossRef]
73
Kalivas PW, Weber B: Ente ea Amphetamine ka har'a ventral mesencephalon e matlafatsa likhoto ho potoloha amphetamine le cocaine. J Pharmacol Exp Ther 1988; 245: 1095-1102
[Lebokose]
74
Vezina P, Stewart J: Amphetamine e tsamaisoa sebakeng sa ventral tegmental empa eseng ho nucleus accumbens e matlafatsa likhoto ho systemic morphine: ho haelloa ke litlamorao. Boko Res 1990; 516: 99-106
[Lebokose]
[CrossRef]
75
Dong Y, Saal D, Thomas M, Faust R, Bonci A, Robinson T, Malenka RC: Tšusumetso e bakoang ke cocoa ea matla a synaptic ho li-dopamine neurons: boitšoaro bo amanang le litoeba tsa GluRA (- / -). Proc Natl Acad Sci USA 2004; 101: 14282–14287
[Lebokose]
[CrossRef]
76
Pittenger C, Kandel ER: Ho batla mekhoa e akaretsang ea polasetiki e tšoarellang nako e telele: aplysia le hippocampus. Philos Trans R Soc Lond B Biol Sci 2003; 358: 757-763
[Lebokose]
[CrossRef]
77
Martin SJ, Grimwood PD, Morris RG: Synaptic plasticity le memory: tlhahlobo ea khopolo-taba. Annu Rev Neurosci 2000; 23: 649-711
[Lebokose]
[CrossRef]
78
Malenka RC: Bokhoni ba nako e telele ba LTP. Nat Rev Neurosci 2003; 4: 923-926
[Lebokose]
[CrossRef]
79
Thomas MJ, Malenka RC: Polasetiki ea Synaptic tsamaisong ea mesolimbic dopamine. Philos Trans R Soc Lond B Biol Sci 2003; 358: 815–819
[Lebokose]
[CrossRef]
80
Kauer JA: Mekhoa ea ho ithuta ka ho lemalla: polasetiki ea synaptic sebakeng sa ventral tegmental ka lebaka la ho pepeseha lithethefatsi tsa tlhekefetso. Annu Rev Physiol 2004; 66: 447-475
[Lebokose]
[CrossRef]
81
Wolf ME, Mangiavacchi S, Sun X: Mekhoa eo li-receptor tsa dopamine li ka susumetsang polasetiki ea synaptic. Ann NY Acad Sci 2003; 1003: 241–249
[Lebokose]
[CrossRef]
82
Malinow R, Malenka RC: Khoebo ea AMPA receptor le polasetiki ea synaptic. Annu Rev Neurosci 2002; 25: 103-126
[Lebokose]
[CrossRef]
83
Li Y, Kolb B, Robinson TE: Sebaka sa liphetoho tse bakoang ke amphetamine ho bongata ba methapo ea dendritic ho li-spiny neurons tse mahareng ho li-nucleus accumbens le caudate-putamen. Neuropsychopharmacology 2003; 28: 1082–1085
[Lebokose]
84
Robinson TE, Kolb B: Liphetoho ho morphology ea li-dendrites le likhahla tsa dendritic ho li-nucleus accumbens le prefrontal cortex kamora ho phekoloa khafetsa ka amphetamine kapa cocaine. Eur J Neurosci 1999; 11: 1598-1604
[Lebokose]
[CrossRef]
85
Tšepo BT, Nye HE, Kelz MB, Self DW, Iadarola MJ, Nakabeppu Y, Duman RS, Nestler EJ: Ho kenyelletsoa ha moaho o tšoarellang oa AP-1 o entsoeng ka liprotheine tse kang tsa Fos bokong ka k'hok'heine e sa foleng le kalafo e meng e sa foleng . Neuron 1994; 13: 1235-1244
[Lebokose]
[CrossRef]
86
Berke JD, Paletzki RF, Aronson GJ, Hyman SE, Gerfen CR: Lenaneo le rarahaneng la ponahalo ea liphatsa tsa lefutso tse bakiloeng ke tšusumetso ea dopaminergic. J Neurosci 1998; 18: 5301-5310
[Lebokose]
87
Silva AJ, Kogan JH, Frankland PW, Kida S: CREB le mohopolo. Annu Rev Neurosci 1998; 21: 127-148
[Lebokose]
[CrossRef]
88
Lonze BE, Ginty DD: Ts'ebetso le taolo ea lintlha tsa sengoloa tsa lelapa la CREB tsamaisong ea methapo. Neuron 2002; 35: 605-623
[Lebokose]
[CrossRef]
89
Konradi C, Cole RL, Heckers S, Hyman SE: Amphetamine e laola polelo ea liphatsa tsa lefutso ho rat striatum ka transcript factor CREB. J Neurosci 1994; 14: 5623-5634
[Lebokose]
90
Konradi C, Leveque JC, Hyman SE: Amphetamine le dopamine e hlohlelletsoang ke polelo ea liphatsa tsa lefutso kapele ho li-neuron tsa striatal ho latela li-receptor tsa NMDA le calcium. J Neurosci 1996; 16: 4231-4239
[Lebokose]
91
Steiner H, Gerfen CR: Dynorphin e laola likarabo tsa D1 dopamine receptor-mediated in the striatum: menehelo e lekanyelitsoeng ea mekhoa ea pele le ea postynaptic ho dorsal le ventral striatum e bonts'itsoeng ke ho fetoloa ha liphatsa tsa lefutso kapele-pele. J Comp Neurol 1996; 376: 530-541
[Lebokose]
[CrossRef]
92
Hurd YL, Herkenham M: Liphetoho tsa limolek'hule ho neostriatum ea batho ba lemaletseng koae. Synapse 1993; 13: 357-369
[Lebokose]
[CrossRef]
93
Cole RL, Konradi C, Douglass J, Hyman SE: Ho ikamahanya le Neuronal ho amphetamine le dopamine: mekhoa ea limolek'hule ea prodynorphin gene regulation ho rat striatum. Neuron 1995; 14: 813-823
[Lebokose]
[CrossRef]
94
Spanagel R, Herz A, Shippenberg TS: Ho hanyetsa li-opioid tse matlafatsang tse sebetsang ka mokhoa o ts'oanang li hlophisa tsela ea mesolimbic dopaminergic. Proc Natl Acad Sci USA 1992; 89: 2046-2050
[Lebokose]
[CrossRef]
95
Carlezon WA Jr, Thome J, Olson VG, Lane-Ladd SB, Brodkin ES, Hiroi N, Duman RS, Neve RL, Nestler EJ: Taolo ea moputso oa cocaine ke CREB. Saense 1998; 282: 2272-2275
[Lebokose]
[CrossRef]
96
Spangler R, Ho A, Zhou Y, Maggos CE, Yuferov V, Kreek MJ: Taolo ea kappa opioid receptor mRNA bokong ba rat ka "binge" ea tsamaiso ea k'hok'heine le khokahano le preprodynorphin mRNA. Boboko Res Mol Brain Res 1996; 38: 71-76
[Lebokose]
97
McClung CA, Nestler EJ: Taolo ea polelo ea liphatsa tsa lefutso le moputso oa k'hok'heine ke CREB le deltaFosB. Nat Neurosci 2003; 6: 1208-1215
[Lebokose]
[CrossRef]
98
Deroche-Gamonet V, Belin D, Piazza PV: Bopaki ba boits'oaro bo ts'oanang le joala ho rat. Saense 2004; 305: 1014-1017
[Lebokose]
[CrossRef]
99
Vanderschuren LJ, Everitt BJ: Ho batla lithethefatsi ho fetoha ntho e qobelloang kamora ho ipusa nako e telele ea cocaine. Saense 2004; 305: 1017-1019
[Lebokose]
[CrossRef]