PMCID: PMC2214707
Sehlooho sena se bile teng e boletsoeng ke lihlooho tse ling ho PMC.
inahaneloang
Ho pepesetsoa lits'oants'o tse fapaneng tsa khatello ea kelello ho ka mpefatsa likoluoa tsa neuropsychiatric, ho kenyeletsa le ts'ebeliso ea lithethefatsi. Bokhoba ba bokuli ke bokuli bo sa foleng ba 'mele moo batho ba sa khoneng ho laola litlhoko tsa bona tsa lithethefatsi, leha ho e-na le litlamorao tse mpe tsa bophelo bo botle. Boko ba batho ba lemalloang bo fetotsoe 'me bo arabela ka tsela e fapaneng haholo khatello ea maikutlo ho feta ea batho ba sa lemeleng. Thutong ena, re totobatsa tse ling tsa litlamorao tse tloaelehileng tsa khatello ea maikutlo le lithethefatsi tsa tlhekefetso ho potoloha le nako ea ts'ebeliso ea lithethefatsi. Re boetse re bua ka lithuto tsa liphoofolo le tsa batho tse fanang ka maikutlo a hore ho phekola likarolo tse amanang le khatello ea lithethefatsi ho ka ba karolo ea bohlokoa ho tlatseng tulo ea nako e telele ho tloha bothateng bona.
Selelekela
Ts'ebeliso e mpe ea lithethefatsi ke e 'ngoe ea mathata a mantlha a bophelo bo botle ba 3 United States mabapi le litšenyehelo tsa tlhokomelo ea moruo le ea bophelo bo botle. Ts'ebeliso e qobelloang ea lithethefatsi leha e ka ba le litlamorao tse mpe tse mpe e hlalosa bokhoba ba ho kula joalo ka bokuli ba kelello (1). Ho fihla joale, ho na le meriana e fokolang haholo e sebetsang ea ho phekola lefu lena. Bokhoba ba tahi ha bo khetholloe joalo ka ketsahalo e le 'ngoe, empa ho fapana le ketsahalo ea liketsahalo tse qalileng ke litlamorao tse matla tsa lithethefatsi tse lateloang ke phetoho ea ts'ebeliso e mpe ea lithethefatsi (Setšoantšo. (Figure1) .1). Bacha ba bangata ba lemalla ho itlopa joala, empa khafetsa ho oela hape ho ts'ebeng lithethefatsi tse sa foleng. Tloaelo ea cyclical ea ts'ebeliso e mpe ea lithethefatsi, e kenyang linako tsa ho khaotsa ho sebelisa lithethefatsi le ho khutlela morao hape, e totobatsa boteng ba lefu lena bophelong bohle ba motho. Patlisiso ea liphoofolo le lipatlisiso tsa batho tsa ho nahana ka batho li thathamisitse ho potoloha ha boko ho sebelisang thepa ea pele e ruisang lithethefatsi (1); leha ho le joalo, mekhoa ea limolek'hule le ea cellular e ikarabellang bakeng sa nts'etsopele le ho phehella ha mmuso o lemaletseng e lula e le thata. Leha mabaka a mangata a ka kenya letsoho ts'ebelisong ea lithethefatsi tsa pele le tse tsoelang pele, ho pepesetsoa khatello ea kelello kapa ea mmele nako efe kapa efe mokhatlong oa bokhoba ba lithethefatsi ho bonahala ho mpefatsa bokuli, ho matlafatsa boits'oaro bohle bo batlang lithethefatsi, ho kenyelletsa ho nka lithethefatsi, ho lakatsa lithethefatsi le ho khutla hape.2, 3). Tlhahlobo ena e fana ka lintlha tse kopaneng tsa khatello ea maikutlo le lithethefatsi 'me e bua ka liphetoho tsa limolek'hule le tsa cellular tse tloaelehileng ho pepesoa khatello ea maikutlo kapa lithethefatsi tsa tlhekefetso. Ntle le moo, ho buisanoa ka mekhoa ea morao-rao ea kalafo e sebelisetsoang ho phekola bokhoba ba tahi, haholo-holo e bakang khatello ea maikutlo.
Bry circry, khatello ea kelello le bokhoba ba lithethefatsi
Mesolimbic dopamine tsela.
Lithethefatsi tsohle tsa tlhekefetso li fana ka litlamorao ho moputso oa mesolimbic dopamine tseleng, e nang le dopamine neurons e simolohang sebakeng sa ventral tegmental (VTA) le ho fetela ho nucleus accumbens (NAc) le preortalal cortex (PFC) (Setšoantšo. (Figure2) 2) (4). Li-stimulants tsa Psychomotor, joalo ka koae, amphetamine, opiate, nicotine le joala, ntle le moputso oa tlhaho, joalo ka thobalano le lijo, li baka ho lokolloa ha dopamine ho NAc ho sa tsotelehe mohato oa bona oa ts'ebetso (5). Ho na le lintlha tse 'maloa tse bontšang hore tsela ea moputso oa mesolimbic dopamine e boetse e sebetsana le khatello ea maikutlo. Taba ea mantlha, mehlaleng ea liphoofolo, ho pepesetsoa khatello ea maikutlo ka mokhoa o hlakileng, joalo ka footshock (6) le pinch (7), e hlahisa keketseho ea tokollo ea dopamine ho NAc. Taba ea bobeli, ho pepesehela lithethefatsi tsa tlhekefetso kapa khatello ea maikutlo ho hlahisa liphetoho tse tšoanang ho electrophysiology ea li-neuron tseleng ea meputso ea mesolimbic dopamine ho liphoofolo. Khokahano e matlafatsang ea phetisetso ea synaptic, joalo ka ha e bonahatsoa ke keketseho ea tšebetso ea glutamate receptor, e etsahala ho li-neurons tsa VTA dopamine kamora ho pepesetsoa khatello ea maikutlo kapa e 'ngoe ea lithethefatsi tse' maloa tsa tlhekefetso, ho kenyelletsa cocaine, nikotini, le joala (8). Kamora nako, khatello ea maikutlo le lithethefatsi tsa tlhekefetso li baka phetoho mokhoeng o khethehileng oa li-neuron tse bitsoang dendrites (9-11). Likhoto tse tlisoang ke khatello ea khatello ea khatello ea maikutlo tse fokotsehang li fokotseha lekaleng la dendritic ho PFC ea kalafo (11). Liphetoho ho lekala la dendritic le tsona li bonoa kamora ho pepesetsoa hoa lithethefatsi tse lemalloang, ka keketseho e hlahang kamora ho pepesetsoa ha koae le amphetamine, athe litokollo tsa makala tsa makala li etsahala kamora ho pepesetsoa morphine (9, 10). Ka bobeli, liphumano tsena li bonts'a hore khatello ea maikutlo le lithethefatsi tsa tlhekefetso li sebetsa ka mokhoa o ts'oanang ho ama methapo ea kutlo, li-electrophysiology le morphology ea li-neurons tse kenyelletsang tseleng ea moputso.
Liphetoho tsa limolek'hule tse amanang le ho pepesetsoa khatello ea maikutlo le bokhoba ba lithethefatsi le tsona li tsoana. Ka lebaka la mofuta o tšoarellang oa ho lemalla, liphetoho lipuong tsa lefutso li ka hlokahala bakeng sa nts'etsopele le phehello ea lefu lena. Liprotheine tse boemong bo botle ba ho fetola liphetoho tsena tsa nako e telele ke batsamaisi ba liphatsa tsa lefutso. Bopaki bo bongata bo bonts'a hore setho sa lelapa la leucine zipper la lintlha tse ngotsoeng, FosB (haholoholo, sebopeho sa protheine ena, ΔFosB), se ipokella tsamaisong ea NAc e latelang ea lithethefatsi tsa tlhekefetso litoeba (12). Ka mokhoa o ts'oanang, khatello ea maikutlo e sa foleng e eketsa maemo a ΔFosB ho NAc le ka pele cortex le amolgdala ea basolateral (13). Setho se seng sa sehlopha sena, se fanang ka karabo ea cAMP - CREB, le sona se khona ho sebetsa ha 'mele o amohela moputso oa lithethefatsi. CREB e laoloa ke kalafo e matla le e sa foleng ea lithethefatsi hohle libakeng tsa moputso oa boko (14, 15). Matšoenyeho a fapaneng, a kenyelletsang ho tsitsipana, ho thatafalloa ho pheta-pheta, le ho sesa ka mokhoa o qobelloang, ho kenya tshebetsong maqhubu a hypothalamic-pituitary-adrenal (HPA) mme a amana le phosphorylation ea CREB libakeng tse 'maloa tsa boko (16), ho kenyelletsa NAc (17). Ntle le moo, mochini o hatisang o amanang le CREB, mohatelli oa element ea cAMP ea sa sebetseng, o bonts'a liphetoho tse tšoanang tsa mRNA ho NAc kamora tsamaiso ea amphetamine kapa ho pepesehela khatello ea maikutlo (18). Kahoo, khatello ea maikutlo le lithethefatsi tse lemalloang li ka sebetsa ka mochine o tloaelehileng oa limolek'hule tse tšoanang le tsa moea ho ntšetsa pele potoloho ea ho lemalla. Leha ho le joalo, lipatlisiso tse eketsehileng lia hlokahala ho fumana hore na lithethefatsi le khatello ea maikutlo li laola mefuta e tšoanang ea sepheo e theohelang litsing tsena tsa li-transcriptal.
Mokokotlo oa HPA.
Boholo ba khatello ea maikutlo bo fana ka litlamorao ho HPA axis, tsela ea mantlha ea khatello ea kelello. Corticosterone-releasing factor (CRF) e patiloe ho subregion ea hypothalamus e tsejoang ka hore ke patricricular nucleus ea hypothalamus (PVN) ho khothaletsa tlhahiso ea li-hormone tsa adrenocorticotropin (ACTH). Kamora ho lokolloa ha eona ho pituitary ea ka ntle, ACTH kamora moo e phahamisa secretion ea adrenal glucocorticoids - cortisol bathong le corticosterone ho liphoofolo - ho kenella maling. (Figure2) .2). Ho se sebetse hantle ha potoloho ena ea khatello ea maikutlo ho kenyelletsa mafu a fapaneng a amanang le khatello ea maikutlo le phallo ea kelello.19).
E ts'oanang le mesolimbic dopamine tsela, axis ea HPA e kenngoa ka litoeba le litempele tse seng tsa botho tse latelang taolo e matla ea lintho tse ngata tse lemalloang - ho kenyeletsa cocaine, amphetamine, ethanol, opiates, le nikotine - mme e baka maemo a ACTH le corticosterone a mangata ka plasma (20). Tsamaiso e sa feleng ea lithethefatsi tsa tlhekefetso mefuteng e tšoanang ea liphoofolo e etsa hore ho be le keketseho e tsitsitseng ea ts'ebetso ea axPA ea HPA, maemong a cocaine le amphetamine, kapa phello e fokotsoang ea litlamorao tsa ts'ebetso ea lithethefatsi maemong a morphine, nikotini , le joala (21-24). Lithuto tsa batho li bonts'a lits'oants'o tse tšoanang kamora ts'ebeliso e seng molaong ea lithethefatsi, ka liphapang tse fokolang. Joalo ka mehlala ea liphoofolo, tsamaiso e matla ea koae (25), joala (26), le nicotine (27) e eketsa maemo a cortisol, athe ho pepeseha ka matla ho opiates ho fokotseha maemo a cortisol (28, 29). Ho kenya tshebetsong ha axis ea HPA ho bolokoa ho lithethefatsi tsa koae.30), athe ts'ebeliso ea ts'ebetso ea opiate e sa foleng, likarabo tsa HPA li fokotseha ha nako e ntse e feta (31), karabelo e atisang ho hlaha ha motho a pepesetsoa khatello ea maikutlo (khafetsa)32, 33). Leha ho le joalo, ha ho hlake hore na ho hloka toka ho ileng ha bonoa mokokotlong oa HPA ka mor'a ts'ebetso ea lithethefatsi ho bontša ho ba kotsing ea ho lemalla kapa ke lebaka la ho pepeseha ha lithethefatsi nako e telele.
Extrahypothalamic CRF.
Ntle le ts'ebetso ea axis ea HPA, CRF e ka kopanya neurotransication kahare ho CNS. Ho beoa ha CRF le li-receptor tsa eona, CRF receptor 1 (CRFR1) le CRFR2, ho pholletsa le systemic ea limbic le neocortex e fana ka maikutlo a karolo ea bohlokoa bakeng sa peptide ena mathateng a amanang, ho kenyelletsa khatello ea maikutlo, ho tšoenyeha, hape, morao-rao, temallo (34). Polelo ea CRF e fetoloa ke tsamaiso ea lithethefatsi tse mpe le tse sa foleng (34) le ka ho ikhula ho sethethefatsi se lematsang. Cocaine, morphine, le joala li tloaetse ho phahamisa polelo ea CRF ka mokhoa o hlakileng; leha ho le joalo, mokhoa oo polelo ea CRF e fetoloang ka mokhoa o sa lekanyetsoang mme ho latela ho khaotsa ho lithethefatsi tsena tse fapaneng ho latela sebaka sa boko le ho ithutela lithethefatsi (ref. 34 le Table Tafole1) .1). Le ha batho ba tsubang hangata ba tlaleha ho imoloha ha khatello ea kelello joalo ka lebaka le susumetsang ts'ebetsong ea koae e tsoelang pele, ha ho na lintlha tse ngata tse hlalosang phello ea nicotine makaleng ana a CRF, haholo litlamorao tsa tsamaiso ea nikotine e bohloko le e sa foleng. Nakong ea ha nicotine e tlosoa, ts'ebetso e eketsehileng ea lisele tse nang le CRF ho PVN e bonoa (35), le litekanyetso tse eketsehang tsa CRF li tlalehiloe kamora ho khaotsa ho litoeba ho lumelloang ho tsamaisa nicotine (36). Phapang ea polelo ea CRF lipakeng tsa sehlopha sa lithethefatsi e totobatsa mekhoa e ikhethileng ea theknoloji le limolek'hule ho CNS eo setheo se seng le se seng se se sebelisang ho hlahisa thepa ea eona e lemalloang. Ntle le moo, liphetoho tse teng liprotheine tsa CRF le mRNA tse hlokometsoeng nakong ea ho khaotsa li fana ka maikutlo a hore tsamaiso ea lithethefatsi e baka liphetoho le ho fetoleloa ha lithethefatsi nako e telele kamora ho pepesetsoa lithethefatsi.
Li-circuits tse ling tsa boko.
Leha Tlhahlobo ena e shebile karolo ea liphatlalatso tsa khatello maemong a bokhoba, ho tlameha ho hlokomeloe hore litsela tsena ha li aroloe ke tšebetso ea tsona. Sistimi ea CRF e bohareng, potoloho ea khatello ea maikutlo ea HPA, le tsela ea moputso oa mesolimbic kaofela e tsoelapele ho ts'oaroa kapa ho hatelloa ke tšebelisano e rarahaneng le lits'ebetso tse ling, ho kenyelletsa le li-system tsa endiogen opioid le noradrenergic (37, 38), tseo ka bobeli li bohlokoa ho loantšeng khatello ea maikutlo le likarabo tsa lithethefatsi. Ntle le moo, likarolo tse ngata tsa boko ho pholletsa le CNS li fetoloa ka mokhoa o sebetsang ha li pepesetsoa lithethefatsi tsa tlhekefetso. Ka hona, khokahano ho pholletsa le boko e hloka ho sebetsoa ka botlalo ha re ntse re tsoela pele ho khetholla methapo ea limolek'hule e tlatsetsang tlasa ts'ebetso le karolo eo khatello e e phethang morerong ona.
Phello ea khatello ea maikutlo molemong oa ho lemalla
Batho ka bomong ba nang le mathata a kelello a amanang le khatello ea kelello, a joalo ka matšoenyeho le khatello ea maikutlo, hangata ba etsa mofuta o itseng oa tšebeliso ea lithethefatsi. Ntle le moo, ho pepesetsoa liketsahalo tse sithabetsang tsa bophelo, tse kang tlhekefetso ea mmele kapa thobalano (39), e hokahanngoa le keketseho ea nicotine, joala le ts'ebeliso ea koae (40). Haufinyane, phuputso e bonts'itse hore ha tlhekefetso e le kholo ho feta bongoaneng (ke hore, ha nako e telele e tsoela pele), ho ka etsahala hore sehlooho se be le temallo ea lithethefatsi hamorao bophelong (41). Ntle le moo, ho pepesetsoa khatello ea maikutlo ho ka eketsa ts'ebeliso ea lithethefatsi hona joale le ho khutlisetsa mekhoa e mebe ea ho nka lithethefatsi (2, 3). Le ha khatello ea maikutlo e sa foleng e ka hlahisa phetoho tahlelong ea boima ba 'mele hammoho le litlamorao tsa tlhaiso le litlamorao, bohlokoa ba liphetoho tse mabapi le tlokotsing ea boits'oaro ba bokhoba ha bo hlahisoe ka mokhoa o hlophisehileng. Leha ho le joalo, lipono tse amanang le batho tse bontšang hore khatello ea maikutlo li ka ama mekhahlelo e fapaneng ea potoloho ea ts'ebetso ea ts'ebeliso e tšehetsoa ke bopaki bo tsoang liphuputsong tsa liphoofolo. Ntle le moo, lithuto tsena tsa liphoofolo li matlafalitse bokhoni ba rona ba ho etsa lipatlisiso ka methati le sepheo sa limolek'hule tse kenyelletsang khokahanong lipakeng tsa khatello ea maikutlo le bokhoba ba tahi.
Ho fumana ts'ebeliso ea lithethefatsi.
Ho fumana ho hlalosoa e le mokhoa oa pele oa ho hlahisa lithethefatsi tsa tlhekefetso ka tsoelo-pele ea tšebeliso e sa feleng. E se e le nako e telele e kholoa hore ho pepesehela ketsahalo kapa boemo bo sithabetsang ho ka eketsa sekhahla sa ho fumana ts'ebeliso ea lithethefatsi. Mefuteng ea liphoofolo, ho pepesetsoa khatello ea 'mele le khatello ea maikutlo, ho kenyelletsa le boikhethollo sechabeng, mohatla o tsitsitseng le footshock, ho ka ntlafatsa taolo ea pele ea amphetamine le cocaine self (42-44). Ntle le moo, ho pepesetsoa khafetsa khatellong ea khatello ea ho sesa ho ka eketsa melemo ea koae (45). Lithuto tsena li fana ka khatello ea maikutlo ho fetoleng litlamorao tsa melemo ea lithethefatsi tse lemalloang.
Ho lokolloa ha Corticosterone ka axis ea HPA ho bohlokoa ho fumaneheng ha taolo ea lithethefatsi. Ho thibela tlhahiso ea corticosterone ke adrenalectomy kapa kalafo ea pharmacologic e thibela tsamaiso ea cocaine ho litoeba (46, 47). Ntle le moo, ho lokolloa ha corticosterone ho latela taolo ea lithethefatsi ho likhoto ho eketsa ts'ebetso ea neuronal ka holim'a maemo a bohlokoa a hlokahalang bakeng sa ho itaola48). Ts'ebetso ena ea "neuronal activation" ea HPA axis e bonahala haholo litekong tse tlase tsa cocaine, hoo litekanyetso tse sa tsoeleng moputso li se li tsamaisoa habonolo. Liphetho tsena li lumellana le phuputso e ileng ea hlahloba maemo a corticosterone ho litoeba tse bontšang likarabo tse fapaneng tsa boitšoaro le endocrine ho tikoloho e ncha (49). Likhoto tse bonts'itseng ts'ebetso ea locomotor le maemo a phahameng a corticosterone ha a pepesetsoa tikoloho ea lipale e ne e bitsoa ba arabelang holimo, athe ba arabelang tlaase ba bonts'itse mesebetsi ea locomotor le maemo a tlase a corticosterone. Kamora mokhoa ona oa ho qala, liphoofolo li ile tsa koetlisetsoa ho sebelisa k'hok'heine. Batho ba arabileng hanyane ha baa ka ba ithuta ho sebelisa k'hok'heine, athe bolaoli bo matla bo ile ba bonoa litlalehong tse hlahlojoang e le ba arabelang holimo. Ho khahlisang, tsamaiso ea corticosterone ea letsatsi le letsatsi e susumetsa le ho boloka tsamaiso ea amphetamine mefuteng e sa arabeng, ba fetola boitšoaro ba bona ho ba ba arabelang holimo (49).
Bokhoni ba corticosterone ba ho fetola moputso oa koae bo ka hokahanngoa le li-glucocorticoid receptors (GRs) tse fumanehang ho li-neurons ho pholletsa le tsela ea moputso oa mesolimbic dopamine (50). Liphoofolo tse fuoeng adrenalectom li bonts'a karabo ea dopamine e sa bonahaleng ho NAc kamora ho pepesetsoa lithethefatsi (51) kapa khatello ea maikutlo (7). Corticosterone e ncha e thibela ho amoheloa ha karabelo ea dopamine. Ho feta moo, li-antagonists tsa GR li fokotsa litekanyetso tsa dopamine tsa extracellular ho NAc ka 50% (52), joalo ka phokotseho e bonoang ka mora adrenalectomy (51). Ntle le moo, bahanyetsi ba GR ba kenang ka har'a VTA ba fokotseha keketseho e susumetsoang ke morphine e susumetsoang ke ts'ebetso ea locomotor (52), ho bonts'a hore ts'ebetso ea li-GR ho VTA e ka buisana le litlamorao tsa ts'ebetso tse itšetlehileng ka dopamine. Ho khahlisang ke hore, litoeba moo gene e kenyang GR e ileng ea hlakoloa ka ho khetheha ho CNS, ho ile ha bonoa ho fokotseha ho thehiloeng hoa tekanyetso ea khothalletso ea ho sebelisa k'hok'heine (53). Liphetho tsena li fana ka maikutlo a hore keketseho ea dopamine e bonoe literekeng tse latelang kamora ts'ebetso ea lithethefatsi (51) kapa khatello ea maikutlo (7) e itšetlehile, bonyane ka karolo, ho lokolloeng ha corticosterone ho tloha axis ea HPA le ts'ebetsong e latelang ea GR.
Karolo ea CRF ea ho fumana moputso oa lithethefatsi ha e so ka e fuputsoa ka botlalo. Prote ea protheine ea CRF le mRNA li fetoloa ka mor'a ts'ebetso e mpe ea lithethefatsi tse ngata tse lemalloang (34). Boithuto bo sebelisang bahanyetsi ba CRFR1 ba bonts'a ho kenya letsoho ha bona litlamorao tsa boitšoaro le litloaelo tsa biochemical tsa koae. Mohlala, blockade ea pharmacological ea CRFR1 e thibela ho lokolloa ha dopamine ea cocaine-induction (54) hammoho le phokotso mefuteng e ruisang ea cocaine (54) le litlamorao tse sebetsang tsa locomotor (54, 55). Lithuto tsena li supa karolo ea CRF ho fetoleng litlamorao tsa lithethefatsi tse tlatsetsang, empa ho hlokahala lithuto tse ling ho tseba hantle karolo ea CRF kholisong ea bokhoba ba lithethefatsi.
A khaotsa ho tsuba.
Litla-morao tsa khatello ea maikutlo moetlong oa khatello ea maikutlo li ntse li latela kamora ho khaotsa ho sebelisa lithethefatsi, ka ho tlohela hanghang le ka nako e telele. Ho kenya letsoho ha axis ea HPA, joalo ka ha ho pakoa ke keketseho e tšoaileng ea litekanyetso tsa corticosterone, ho etsahala kamora ho khaotsa ho matla lithethefatsing tse ngata tsa tlhekefetso bathong le mehlaleng ea liphoofolo (20). Ho khahlisang ke hore, kamora ts'ebetso ena ea ts'ebetso ea pele, maemo a basal corticosterone le cortisol a khutlela ho tloaelehileng ho batho le litoeba, ka ho latellana (20). Leha ho le joalo, nakong ea ho tlohela nako e telele ho li-psychostimulants le opiates, axis ea HPA e bonts'a karabelo e matlafalitsoeng ha e pepesetsoa khatello ea maikutlo. K'hok'heine ea mehleng56) le bokhoba ba opiate (57), maemo a eketsehang a ACTH le cortisol a ne a lekantsoe ka mora ts'ebetso ea metyrapone ea lik'hemik'hale. Metyrapone e thibela motsoako oa cortisol, e sitisa karabo e tloaelehileng ea cortisol ho hypothalamus ebe ka tsela eo e baka ts'ebetso ea tsela ea khatello ea HPA (20). Ntle le moo, ho basebelisi ba koae ba koahelang, ho se tsotelle ho sithabetsang maikutlong le 'meleng, hammoho le takatso e matla ea lithethefatsi, hoa bonoa (58), e lumellanang le axis e fetotsoeng ea HPA. Ho litoeba, nakong ea ho khaotsa ho matla, likarabo tsa corticosterone li matlafatsoa ha li pepesetsoa khatello ea maikutlo (1).59). Lintlha tsena li fana ka maikutlo a hore karabelo ea khatello ea maikutlo e ka lemohuoa ka ho pepesetsoa ha lithethefatsi le ho khaotsa kamora moo. Ho fapana le hoo, bopaki ba morao-rao bo bonts'itse karabelo e lumellaneng ea khatello ea maikutlo nakong ea ha nicotine e tsoa ho liphoofolo. Maemo a Corticosterone a ne a le tlase haholo ho litoeba tse pepesitsoeng khatello ea khatello nakong ea ho khaotsa nicotine, leha maemo a bona a basal corticosterone a ne a tšoana (60). Ba tsubang ba sa foleng ba bonts'a secretion e atolositsoeng ea cortisol (61, 62), le phokotso ea cortisol kamora ho tsuba ho khaotsoe ho amahanngoa le ho teba ha ho khaola le ho khutla hape (63, 64). Ka kopanelo, lithuto tsena li bonts'a liphetoho lipakeng tsa karabelo ea HPA ho motho ea sithabetsang maikutlo nakong ea ho khaotsa ka nako e telele, e ka nkang karolo ea bokhoni ba khatello ea ho khutlisetsa lithethefatsi hantle ka mor'a hore moriana o tlosoe.
Liphetoho maemong a CRF peptide le mRNA ho pholletsa le CNS li bonoa kamora ho khaotsa ho matla lithethefatsong tse 'maloa tsa tlhekefetso, ho kenyelletsa koae le opiates,' me liphetoho tsena li fapana ka sebaka sa boko le ts'ebeliso ea lithethefatsi. Ho khahlisang, ho eketseha ha CRF mRNA kahare ho PVN e nang le ho eketseha ha boits'oaro nakong ea ethanol, cocaine le ho tlosoa ha morphine (65-67). Ntle le moo, blockade ea CRF system le bahanyetsi kapa li-antibodies e fokotsa matšoenyeho a bonoang karolong ena e mpe ea ho tlohela (65-67). Bohanyetsi ba CRFR1 bo fokotse matšoao a mmele a ho tlosoa ha morphine ho likhoto tse itšetlehileng (67). Ka bobeli, tlhaiso-leseling ena e bonts'a hore mokhoa oa CRF o bapala karolo ea kelello le matšoao a ho tlosoa ka matla lithethefatsing tse tlatsetsang. Le ha ho le joalo, karolo ea CRF kapa khatello ea maikutlo maemong a ho tlosoa ha nako e telele ha e e-so hlakisoe.
Phetisetso ea ho batla lithethefatsi.
Likhopolo tse ngata tsa bokhoba ba tlhekefetso bo tiisa hore khatello ea maikutlo ke e 'ngoe ea lisosa tsa mantlha tsa ho khutlela mokhoeng oa batho ba lithethefatsi (2, 3). U sebelisa mehlala ea liphoofolo, li-laboratori tse 'maloa li bontšitse hore ho pepesehela khatello ea maikutlo e matla ho ka khutlisa ho ts'oara lithethefatsi tse fapaneng, ho kenyeletsa opiates, psychostimulants, joala le nikotine (68-71). Khatello ea kelello e thusa ho khutla ka ho etsa tšebetso ea methapo ea kelello ea CRF. Liphoofolo tse koetliselitsoeng ho sebelisa lithethefatsi ebe li se li tlositsoe moriana o tobetsa kamorao ho ente ea intracerebroventricular CRF (72). Potoloho e ikhethileng e kenyelletsang CRF ho amygdala e atolositsoeng, sebopeho sa bohlokoa sa boits'oaro bo sebetsang le ts'ebetso, e ntlafalitsoe molemong oa ho boelana hape o bakang khatello ea maikutlo. Meetso e kenyelletsang sebaka se atamelaneng sa amygdala le tsela ea moputso, ho kenyelletsa ntlha e bohareng ea amygdala, moeli oa bethe ea stria terminalis (BNST), le likarolo tsa NAc (Setšoantšo. (Figure2) 2) (73). Bohlokoa ba tsela ena mokhoeng oa ho lemalla ho bonahala haholo ha o khutla hape kapa o khutlisoa hape. Ho kenella ha morero oa CRF ho tloha amygdala e bohareng ho ea BNST ho thibela khatello ea maikutlo (mohlala, ka footshock) ho khutlisetsa koae (74, 75), le liente tsa selehae tsa D-Phe, mohanyetsi oa CRF receptor antagonist, ea BNST, empa eseng amygdala, e fumana ho khutlisetsoa hoa sepheo sa (75). Ka ho khetheha, li-CRFR1 tsa sebakeng seo li fumanehang ho BNST, empa eseng amygdala kapa NAc, li boetse li khutlisetsa khatello ea maikutlo ho ts'ebelisong le lithethefatsi (68). Ho khahlisang ke hore, bahanyetsi ba khethiloeng ba CRFR1 ba fumana ho ts'oaroa ha foothock-e susumetsang ho ts'oara koae kapa ho batla opiate (68, 76) empa ha e na phello ea ho khutlisetsoa ka matla ke lithethefatsi (72, 77). Lintlha tsena li bontša hore khatello ea maikutlo ea tsela e nang le CRF, e simolohang ho amygdala le ho kenella BNST, le ts'ebetso e latelang ea CRFR1 e tsebisitsoeng ho BNST, e baka ts'ebeliso ea lithethefatsi ho liphoofolo tse neng li lemaletse pejana.
Haufinyane, CRF e fumanoe ho VTA, sebaka sa tlhaho sa dopamine neurons tseleng ea moputso (78). Ho likotlo ka bobeli tsa koae tse nang le koae le koae, CRF e ntšoa VTA kamora ho putlama ka matla; leha ho le joalo, mohloli oa CRF ena ha o tsejoe (78). Ho liphoofolo tse nang le boiphihlelo ba koae, ke glutamate le dopamine li ntšoa VTA ka kopanelo le CRF ha li sebetsana le khatello ea maikutlo. Ho lokolloa ha glutamate le dopamine ho its'etleha ho CRF le ts'ebetsong e latelang ea li-receptor tsa eona, ha liente tsa lehae tsa bahanyetsi ba CRF ho VTA li bonts'a tokollo ea li-neurotransmitters tsa 2 (78, 79). Ntle le moo, tsamaiso ea bahanyetsi ba CRFR2, empa eseng bahanyetsi ba CRFR1, sebakeng sa heno ho VTA e thibetse bokhoni ba footshock ho khutlisetsa cocaine e batlang morerong oa ho itaola (79). Ha li kopantsoe hammoho, liphuputso tsena li bonts'a karolo ea CRF ho fetoheng mesebetsi ea sele ea dopamine, ka ho latela boiphihlelo ba lithethefatsi.
Leha lithuto li bontšitse ka ho hlaka karolo eo CRF e lokelang ho e etsa ea ho khutlisa takatso ea lithethefatsi tse bakang khatello ea maikutlo, ke ba fokolang haholo ba ileng ba hlahloba hore na mekhoa e meng ea limolek'hule e bohlokoa ho khutlisetsong khatello e tlisoang ke khatello ea maikutlo. Sengoloa sa CREB, se neng se kenelletse khatello ea maikutlo le bokhoba, se sa tsoa bontšoa se kenyeletsa ho khutlisetsoa ho matla kelellong. Litoeba tse haelloang ke CREB ha li bontše ho khutlisetsoa ha khatello ea maikutlo sebakeng sa boemo ba cocaine (70). Leha ho le joalo, litoeba tsena li bonts'a ho khutlisetsoa hoa lithethefatsi ho ea ho lethal dose ea cocaine (70). Khaello ena ea ho khutlisetsoa khatello ea maikutlo le eseng e bakiloeng ke lithethefatsi e bonts'a tlhokahalo e ikhethang ea CREB karabong ea maikutlo e khothalletsoang ea khatello ea lithethefatsi tsa tlhekefetso. Ho khahlisang, mofuta o lebisang oa "CREB" o hlahisang mofuta oa "brain-based neurotrophic factor" (BDNF), o hlophisitsoeng sebakeng sa VTA le NAc ea mesolimbic dopamine moputsong, o ile oa eketseha kamora ho khaotsa ho tsuba koae e sa foleng.80). Keketseho ea BDNF libakeng tsena tsa boko e amanang hantle le karabelo ea litoeba ho lithahasello tse amanang le lithethefatsi (80), le liphuputso tsa morao-rao li bonts'a hore BDNF e ka nolofalletsa ho khutlela mekhoeng ea ho batla lithethefatsi (81). Liteko tse ling tse hlalosang mokhoa oa limolek'hule oa ho imeloa kelellong li hlokahala ho utloisisa ka botlalo ts'ebetso ena e rarahaneng.
Meriana ea phekolo
Ka bobeli lithuto tsa liphoofolo le tsa batho li bontšitse ka mokhoa o hlakileng karolo ea khatello bakeng sa ts'ebetso ea bokhoba bohle. Likhoba tsa litlatsetso li hlalosa khatello ea maikutlo e le e 'ngoe ea mabaka a bohlokoa a ho tsoela pele ho sebelisa lithethefatsi kapa ho khutlela morao ts'ebelisong ea lithethefatsi kamora nako ea ho khaotsa ho tsuba. Ka hona, ho fokotsa ts'ebetso ea khatello ea maikutlo ho potoloha nako eohle ea bokhoba ba tahi, ho bohlokoa haholo nakong ea ho tlohela. Leha ho le joalo, kalafo ea hona joale ea bokhoba ba tahi ha e ea lekana, kaha hoo e ka bang halofo ea batho bohle ba lemaletseng joala hape ba khutlela ho tseng lithethefatsing. Leha maemo a phahameng a ho oela hape, lihlopha tse 'maloa tsa phekolo ea lithethefatsi li ntse li bontša ts'episo ho phekola likarolo tse ling tsa bokhoba ba tahi. Le ha tse ling tsa kalafo tsena li lebisa lits'oants'o tsa khatello le bokhoba ba litumelo, joalo ka lipotoloho tsa CRF tse boletsoeng ka holimo, ba bang ba nkile mokhoa oa ho ngola lits'ebetso tsa bona tsa kalafo, ba shebile lits'ebetso tsa bobeli tse ka fetolang khatello ea maikutlo le mekhoa ea bokhoba.
CRFR1 bahanyetsi.
Joalo ka ha mehlala ea liphoofolo e bontšitse ka ho hlaka, bahanyetsi ba CRFR1 ba sebetsa hantle ho khutlisetsa khatello ea maikutlo e bakiloeng ke khatello ea maikutlo ho tloleng ho sebelisa lithethefatsi (76, 82-84). CP-154,526, mohanyetsi ea sa tsubeng oa CRFR1, o re o khutlela mokhoeng o bakang khatello ea maikutlo o bakang ho batla lithethefatsi ho likhoto (77). Antalarmin, MJL-1-109-2, le R121919, bahanyetsi bohle ba CRFR1 ba sa lateleng lintho tse ngata, ba fokotsa taolo ea ethanol ho likhoto tse itšetlehileng ka ethanol, ntle le ts'ebetso ea ts'ebeliso ea ethanol ho likhoto tse sa tsotelleng (85). Ntle le moo, antalarmin e bontšitsoe e fokotseha maemo a ACTH le corticosterone maemong a seng a botho ho kenyelletsa le ho fokotsa palo ea boits'oaro ba boits'oaro (86). Ka bobeli lintlha tsena li fana ka maikutlo a hore CRFR1 e kanna ea ba sepheo se nepahetseng sa kalafo bakeng sa meriana ho phekola bokhoba ba lithethefatsi. Leha ho le joalo, ho palo ea batho, tsoelo-pele ea ho sebelisa metsoako e lebisang receptor ena kalafong ea bokhoba e bile butle. Hajoale, antalarmin e maemong a I le liteko tsa bongaka tsa karolo ea II bakeng sa kalafo ea ho tšoenyeha le khatello ea maikutlo, leha ho se liphetho tse tsoang liphuputsong tsena tse phatlalalitsoeng (phatlalatsa)87). Ntle le moo, R121919 e bonts'itsoe tlhahlobo ea bongaka e bulehileng hore e sebetse ho fokotsa khatello ea maikutlo le matšoao a kang a ho tšoenyeha ho batho (88, 89), hape haufinyane tjena, CRFR1 antagonist antagonist NB1-34041 e bontšitse katleho ho fumana karabelo e phahameng ea khatello ho liphoofolo le ho batho, empa ha ho na lipatlisiso tse ileng tsa lekola boleng ba kalafo ba likhakanyo tsena ho phekola bongata ba batho ba lemaletseng lithethefatsi (90).
Varenicline.
Ho lumeloa hore Nikotine ke eona ntho e ka sehloohong e ikarabellang bakeng sa tšebeliso e mpe ea ts'ebeliso ea koae. Nicotine e sebetsa ho li-receptor tsa α4β2, tse kenyellelitsoeng lintlheng tse khotsofatsang tsa moriana ona, ka ho toba ka tokollo ea dopamine ho NAc (91). Ka hona, motho ea sa tsotelleng a amohelang receptor ena, ka ho thibela ho kenella ha sethala, a ka nolofatsa matšoao a ho tsoa. Varenicline, cy4β2 acetylcholine nicotinic receptor partition agonist, e bontšitse tšepiso ho lemaletseng bokoali ba nicotine. Joalokaha ho tlalehiloe litekong tse 'maloa tsa tliliniki, litekanyetso tsa ho khaotsa ho tsuba li phahame ho bakuli ba fuoeng varenicline ha ba bapisoa le placebo (92, 93). Matšoao a fokotsehang a ho lakatsa le ho tlohela a boetse a bonoa (92, 94). Ho lithuto tsa liphoofolo, varenicline e fokotsa tsamaiso ea nicotine self (95), le haufinyane tjena, likhoto li bonts'itse ts'ebeliso ea ethanol kamora ho latela taolo e mpe ea varenicline (96). Joalokaha lithuto tsena li bontša, varenicline ke mokhoa o sebetsang oa kalafo bakeng sa ho khaotsa ho tsuba. Leha ho le joalo, ha ho na lithuto tse ileng tsa hlahloba sethethefatsi sena ka ho khetheha nakong ea ho khutlisetsoa mehlaleng ea liphoofolo.
Li-antidepressants.
Ho ipapisitsoe le karolo e ka 'nang ea etsoa ke bahanyetsi ba CRFR1 ho phekola khatello ea maikutlo, mme ha ho fanoa ka hore khatello ea maikutlo e ka fana ka maikutlo le khatello ea maikutlo, meriana e meng ea antidepressant e' nile ea hlahlojoa ho theosa le lilemo bakeng sa ho sebetsa ka thata ho phekoleng tlhekefetso ea lithethefatsi. Bupropion, antidepressant ea atypical, e bonts'itse ts'episo ea bohlokoa kalafong ea ts'ehetso ea nicotine (97). Boiphihlelo ba Bupropion ba ho tlohela ho tsuba bo ile ba bonoa ke ngaka e sa sebetseng e phekolang bakuli ba khatello ea maikutlo (98). Ho tloha ka tlhokomeliso ena e matla, bupropion e bontšitsoe e sebetsa hantle litekong tse ngata tsa bongaka e le moemeli oa ho khaotsa ho tsuba, haholoholo hammoho le phekolo ea phetisetso ea nicotine (98). Bupropion e sebetsa ho baeti ba norepinephrine le dopamine, e thibela ho khutlisa hape ha li-neurotransmitters tsena. Ntle le moo, e sebetsa e le mohanyetsi ho α4β2 nicotinic receptors (99). Haufinyane, phuputso e sebelisoang ho latela mohlala oa methapo ea ho itšetleha ka nicotine e bontšitse ho fokotseha hoa lipontšo tsa 'mele tse amanang le ho ikarola ha nikotine kamora ho tsamaisoa hoa bupropion (100).
Ho li-antidepressants tsa khale, ke desipramine (DMI) feela, e sebelisang antidepressant, e bonts'itseng ts'episo ea ho phekola bokhoba ba koae. Boithuto bo fetileng bo tlalehetse ho fokotseha hoa tšebeliso ea koae ho likhoto tse iphehlang (101) mme e fokotseha ho ho lakatsa ha koae ho batho ho latela kalafo e sa foleng ea DMI (102). Leha ho le joalo, lipatlisiso tsa morao-rao tse lemaletseng bokhoba ba koae li ile tsa bontša ho se na thuso ea kalafo ea DMI (103). Hajoale, DMI ha e sebelisoe hangata ho phekola bokhoba ba koae hobane meriana e meng, joalo ka modafinil, e bonts'a ts'episo e kholo litekong tsa lingaka (98). Mokhoa o nepahetseng oa ts'ebetso ea modafinil ha o tsejoe, leha ho bontšitsoe hore o thibela ho khutlisetsoa ha dopamine le norepinephrine hape le ho kenya ts'ebetsong glutamate le inhibit GABA neurotransmission (104). Ho khahlisang, lisebelisoa tse ling tse lebisang ts'ebetsong ea GABA, haholo-holo tse eketsang ts'ebetso ea GABA, li bontšitsoe li sebetsa hantle ho phekola takatso ea koae le ho khutlela morao (98).
Lofexidine.
Sistimi ea noradrenergic e bile le tšusumetso e matlafatsong e bakiloeng ke khatello ea maikutlo ea ho batla lithethefatsi. Lofexidine, í2 adrenergic receptor agonist, e fokotsa matšoao a ho khaotsa opioid ka ho fokotseha ho hlaha ha noradrenergic ho CNS (105). Mefuta ea liphoofolo e bontšitse hore lofexidine e kenyelletsa mokhoa o matlafatsang oa ho ts'oasa lithethefatsi (footshock).106), joalo ka ts'ebetso ea α2 adrenergic receptor agonists kapa ka mokhoa o ikhethileng oa likhakanyo tsa noradrenergic libakeng tse thibelang tikoloho hantle li thibela ho khutlisetsoa ha khatello ea kelello ho likhoto (106, 107). Ntle le moo, liente tsa lehae tsa bahanyetsi ba Noradrenergic ho BNST le amygdala e bohareng li sitisitse bokhoni ba footshock ho khutlisa ho batla lithethefatsi (108). Ntle le moo, patlisiso ea morao-rao ea motho e bontšitse hore motsoako oa lofexidine le naltrexone, mohanyetsi oa opioid, o ile a eketseha haholo litekanyetso tsa ts'ebeliso ho basebelisi ba opiate ba morao-rao le ho fokotseha ha litakatso tsa khatello ea lithethefatsi ha ho bapisoa le naltrexone feela (109). Le ha lofexidine e amohetse hore e sebelisoe ho tlosoang ka opioid United Kingdom, lithuto tse ling li hlokahala ho tseba ka botlalo karolo e phethoang ke extexidine phosong e bakang khatello ea maikutlo.
Makhopo a mang.
Ho amohetsoe meriana e meng e mengata bakeng sa tlhekefetso ea lithethefatsi bakeng sa kalafo ea joala. Naltrexone e fokotsa litekanyetso tsa ho nooa tsa mantlha hammoho le litakatso tsa joala le palo e akaretsang ea likhutlo tse khutlisetsang ts'ebelisong ea joala (110). Leha ho le joalo, naltrexone ha e sebetse ho thibela ho khutlisetsoa ha khatello ea maikutlo maemong a liphoofolo (111), hape ha e ea sebetsa hantle ho phekoleng takatso e matla ea lithethefatsi ho batho (112). Acamprosate, modula ea N-methyl-D-aspartic acid receptor, e boetse e amoheloa ho phekola ho itšetleha ha joala. E sebelisoa ho thibela ho khutla hape bokhobeng ba joala, ho bontšitsoe hore ho fokotsa tšebeliso ea joala hammoho le ho lakatsa (113). Ntle le moo, acamprosate e fokotsa ho tšoenyeha ho amanang le ho itlopa joala le ho eketsa ho itlopa joala.98). Leha ho le joalo, ha ho tsebe letho ka bokhoni ba acamprosate ba ho thibela ho khutlela morao bocha.
fihlela qeto e
Joalokaha ho bile le ts'oaetso ho batho, 'me joale ho bontšitsoe ka mokhoa o kholisang lithutong tsa liphoofolo, khatello ea maikutlo ke e' ngoe ea lintlha tsa bohlokoa ho tsamaisang moputso o amanang le ho pepesetsoa lithethefatsi qalong. Ntle le moo, khatello ea maikutlo e eketsa ho lakatsa lithethefatsi le ho khutlela morao ho ts'oereng lithethefatsi. Boithuto bo bontšitse khokahano e ntle ea khatello ea maikutlo le takatso ea lithethefatsi ho batho (114), e bonts'ang ts'ebetso ea litsela tsa moputso kamora ho pepeseha khatello ea khatello ea maikutlo (115). Phapang e kholo kutloisisong ea rona ea ts'ebeliso ea lithethefatsi ke hore na liphetoho tse hlahisoang ke k'hemistri ea boko tse lemalloang ho lithethefatsi tse sa feleng li bakoa ke maemo a tikoloho, joalo ka tlhekefetso ea 'mele kapa ea thobalano, e tsejoang e lebisa tšebeliso e seng molaong ea lithethefatsi, kapa tšebeliso e telele ea lithethefatsi ka boyona . Haufinyane tjena, ho bontšitsoe hore batho ba ipolelang ba eketsehile khatello ea bophelo ba bonts'a moputso oa lithethefatsi ho jekeng e mpe ea amphetamine (116), ho ts'ehetsa tšehetso ea maikutlo le ho pepesehela tikoloho e sa foleng ea khatello ea maikutlo ho eketsa kotsi ea ho ba le boitšoaro bo lemalloang. Ntle le moo, sehlopha se nang le khatello e matla ea maikutlo se bontšitse ho fokotseha ha dopamine ho lokolloe ha motheo le ho arabela amphetamine (116), ho bonts'a hore karabelo ena e fokotsehileng ea dopamine e ka baka kotsi ea ho lemalla. Mohlaleng oa litšoene tsa maemo a phahameng sechabeng, palo kapa ho fumaneha ha li-receptor tsa dopamine D2 li ile tsa eketseha ho litšoene tse hlahelletseng, athe ha ho phetoho e hlokometsoeng ho ba batona ba maemo a tlase a likhohlopo (117). Ho khahlisang, koae e ne e matlafatsa le ho feta ho litšoene tse hlaheletseng (117), ho bonts'a hore liphetoho tsa tikoloho tsa sisteme ea dopamine li ka fetola tsietsing ea ho lemalla. Leha ho le joalo, lithuto tsa nako e tlang tse hlahlobang sepheo sa limolek'hule le litsela tse tšoaeang tse fetotsoeng ke khatello ea maikutlo ea tikoloho, ea 'mele le ea kelello le litlamorao tsa tsona boits'oarong bo bobebe li hloka ho phetheloa.
Leha kalafo e sebetsang bakeng sa ts'ebeliso e mpe ea lithethefatsi e kenyelletsa kalafo ea boits'oaro le meriana, lenane la meriana le amohetsoeng ke FDA bakeng sa kalafo ea bokhoba ba tahi le lekanyelitsoe. Ho joalo, hajoale ha ho na meriana e amoheloang ea ho lemalla koae. Ho feta moo, liphekolo tse ngata tse fumanehang li fanoa ha motho a lemaletse ts'ebeliso ea lithethefatsi. Mekhoa ea kalafo ea hajoale ea joala, nikotini le bokhoba ba opiate li sebelisetsoa ho fokotsa kapa ho emisa ho ja joala ba lithethefatsi. Mohlala, naltrexone e fokotsa tšebeliso ea joala, e lumella mokhoa oa bophelo o atlehileng haholoanyane. Bupropion e laetsoe hammoho le kalafo ea motsoako oa nicotine ha bakuli ba ntse ba tsuba. Ke mekhoa e fokolang ea kalafo e boletsoeng nakong ea ho tlohela, haholo ho thibela ho khutla hape. Ho theosa le lilemo tsa ho qetela tsa 10-15, lipatlisiso mabapi le litlamorao tsa khatello ea maikutlo li khethollotse litsamaiso tsa CRP tsa bohareng le tse bohareng e le libapali tsa bohlokoa tsa ho hokahanya khatello le bokhoba. Le ha lithethefatsi tsa kalafo tse lebisang ts'ebetsong ena li ntse li hlahlojoa hore na li sebetsa hantle hakae kalafo, lipatlisiso tse eketsehileng tse hlahlobang ho tlosa le ho khutla, haholo-holo tse bakiloeng ke khatello ea maikutlo, li hlokahala ho hlakisa lipheo tsa kalafo e tlisoang.
lumela hore baa fokola
Bangoli ba lakatsa ho leboha Charles P. O'Brien ka ho bala ka bokhutšoanyane buka ena e ngotsoeng ka letsoho. Mosebetsi ona o tšehelitsoe ke National Institute on Drug Abuse Aid DA116-49-01A2 (ho JA Blendy).
Mongolo o botlaaseng ba leqephe
Likarolo tse senang maikutlo tse sebelisitsoeng: ACTH, hormone ea adrenocorticotropin; BNST, mookotaba oa bethe ea stria terminalis; CREB, karolo ea karabelo ea cAMP-protein e tlamang; CRF, corticosterone-releasing factor; CRFR, CRF receptor; GR, glucocorticoid receptor; HPA, hypothalamic-pituitary-adrenal (axis); NAc, li-bokelle tsa nucleus; PFC, cortex ea pele; PVN, motsoako oa "patothricular" oa "hypothalamus"; VTA, sebaka se khubung ea moea.
Khohlano ea thahasello: Bangoli ba phatlalalitse hore ha ho na khohlano ea phaello e teng.
Tlhahiso ka sengoloa sena: J. Clin. Sebelisa chelete. 118:454–461 (2008). doi:10.1172/JCI33946.
References