Ho lemalla: Mafu a ho qobelloa le ho kenngoa ha Drive ho Orbitofrontal Cortex (2000)

LITLHAHISO: Ena ke kakaretso ea karolo e ka pele ea "cortex" ea ho kenella bokhobeng. Karolo ena ea boko e bua ka taolo ea phethahatso, ho rala le ho fihlela sepheo, hammoho le taolo ea tšusumetso.


HO ITHUTA KA HO FELETSA: Tlatsetso: Lefu la ho Qobella le ho Kenyelletsa Letlapa la Orbitofrontal Cortex

Cereb. Cortex (2000) 10 (3): 318-325. doi: 10.1093 / cercor / 10.3.318

Nora D. Volkow1,3 le Joanna S. Fowler2

+ Lingoliloeng tsa Sengoli

1Medical le

2Chemistry Departments, Brookhaven National Laborator, Upton, NY 11973 le

Seteishene sa Psychiatry, SUNY-Stony Brook, Stony Brook, NY 3, USA

inahaneloang

Ho utloisisa liphetoho tse teng bokong bo bang teng phetohong ho tloha ho bo tloaelehileng ho ea ho ts'ebetsong ea boits'ebetso ho na le litlamorao tse kholo bophelong ba sechaba. Mona re beha taba ea hore leha li-circuits tsa meputso (li-nucleus accumbens, amygdala), tseo esale e le likhopolo tsa bokhoba ba lithethefatsi, e kanna ea ba tsa bohlokoa ho theha boitaolo ba lithethefatsi, mmuso o lematsang o boetse o kenyelletsa ho senyeha ha lipotoloho tse amehang ka boits'oaro bo matla le ho khanna. Re beha taba ea hore dopaminergic activation ea li-circuits tsa meputso e isang tšebetsong ea taolo ea lithethefatsi e lebisa ho se sebetse hoa orbitofrontal cortex ka potoloho ea striato-thalamo-orbitofrontal. Sena se ts'ehetsoa ke liphuputso tse nahannoeng hore ho batho ba sebelisang lithethefatsi hampe ba ithutileng nakong ea ha motho a khaotsa ho sebetsa, "cortex ea orbitofrontal" e sebetsa hantle haholo ha a bapisoa le maemo a dopamine D2 receptors. Ka lehlakoreng le leng, ha batho ba sebelisang lithethefatsi ba lekoa nakoana ka mor'a tšebeliso ea koae kapa litakatso tse tahiloeng tsa lithethefatsi, "cortex" ea orbitofrontal ke hypermetabolic ka tekanyo ea takatso ea eona. Hobane orbitofrontal cortex e ameha ka drive le ka boits'oaro bo phehellang, ts'ebetso ea eona e sa tloaelehang moqoqong o lemaletseng e ka hlalosa hore na hobaneng ts'ebetso e ikemetseng ea lithethefatsi e etsahala le ka ho amohela litlamorao tsa litlamorao tsa lithethefatsi le ho e-na le karabelo e mpe. Moetso ona o bolela hore monyaka ka kotloloho ha oa lekana ho boloka ts'ebetso e qobelloang ea lithethefatsi molemong oa lithethefatsi le hore lithethefatsi tse ka sitisang ts'ebetso ea potoloho ea li-striato-thalamo-orbitofrontal li ka ba molemo ho phekolo ea bokhoba ba lithethefatsi.

Patlisiso mabapi le bokhoba ba lithethefatsi e lebisitse tlhokomelo molemong oa ts'ebetso ea lisosa tsa tlhekefetso. Patlisiso ena e lebisitse ho khethollotsoeng li-circonal tsa neuronal le li-neurotransmitters tse amehang ho matlafatseng lithethefatsi. Bohlokoa bo boholo ho matlafatsong ea lithethefatsi ke sisteme ea dopamine (DA). Ho phatlalalitsoe hore bokhoni ba lithethefatsi tsa tlhekefetso ho eketsa DA libakeng tsa boko ba li-limbic (li-nucleus accumbens, amygdala) bo bohlokoa bakeng sa litlamorao tsa bona tsa ho matlafatsa (Koob le Bloom, 1988; Pontieri et al., 1996). Le ha ho le joalo, karolo ea DA litabeng tsa bokhoba ba lithethefatsi ha e hlake haholo. Hape, leha litlamorao tse matlafatsang tsa lithethefatsi tsa tlhekefetso li ka hlalosa mokhoa oa ts'ebetso oa ts'ebeliso ea lithethefatsi, matlafatso ka mokhoa o le mong ha oa lekana ho hlalosa ts'ebetso e matla ea lithethefatsi le tahlehelo ea taolo ntlheng e lemaletseng. Ebile, ho ipusa ka lithethefatsi ho etsahala le ha ho e-na le mamello ho likarabo tse khahlisang (Fischman et al., 1985) mme ka linako tse ling esita le ho na le litlamorao tse mpe tsa lithethefatsi (Koob le Bloom, 1988). Ho phatlalalitsoe hore bokhoba ba lithethefatsi ke litholoana tsa phetoho tsamaisong ea DA le makaleng a moputso a kenyelletsang ts'ebetsong ea ts'ebeliso ea lithethefatsi ho ea ho botsamaisi ba lithethefatsi bo sa feleng (Dackis and Gold, 1985; EppingJord et al., 1998). Leha ho le joalo, hape ho ka etsahala hore lisekhete tsa boko ntle le tse laolang likarabo tse khahlisang tsa lithethefatsi tsa tlhekefetso li kenelletse ts'ebelisong ea lithethefatsi.

Ha ho sekasekoa hore na ke liserekisi life ntle le tse amehang ts'ebetsong ea moputso, ho bohlokoa ho hlokomela hore matšoao a bohlokoa a bokhoba ba lithethefatsi ho batho ke tšebeliso e mpe ea lithethefatsi le ts'ebetso e kholo ea ho sebelisa lithethefatsi ka litšenyehelo tsa boits'oaro bo bong. (American Psychiatric Association, 1994). Ka hona re fana ka maikutlo a hore lipotoloho tse amehang ka boits'oaro ba drive le boits'oaro bo nang le tiisetso li ameha tšebelisong ea lithethefatsi. Haholo-holo re beha taba ea hore nako le nako tšebetso ea DA ea ts'ebeliso e mpe ea lithethefatsi e baka tšitiso ea tšitiso ea "orbitofrontal cortex" ka potoloho ea striato-thalamo-orbitofrontal, e leng potoloho e kenyang letsoho ho laoleng drive (Stuss le Benson, 1986). Ho se sebetse hantle ha potoloho ena ho fella ka boitšoaro bo qobelloang lithutong tse lemaletseng le tšusumetso e fetelletseng ea ho reka le ho tsamaisa lithethefatsi ho sa tsotelehe litlamorao tsa tsona tse mpe. Khopolo-taba ena e hlophisoa ke liphuputso tse inahaneloang tse bonts'ang ho senyeha hoa kelello tsa "sepriatal, thalamic" kapa "orbitofrontal" libakeng tsa bokhoba ba lithethefatsi (Volkow et al., 1996a). Tlhahlobo ena e akaretsa lithuto tseo tse shebane haholo le cortex ea orbitofrontal le lithutong tsa cocaine le bokhoba ba joala. Tlhahlobo ena e boetse e fana ka litlhaloso tse khutšoane tsa anatomy, ts'ebetso le methapo ea kutlo ea orbitofrontal cortex e amanang le tšebeliso ea maikutlo mme e fana ka mohlala oa mofuta o mocha oa ts'ebeliso ea lithethefatsi o ipiletsang ka bobeli ba ho lakatsa (ho lakatsa, tahlehelo ea taolo, ho nahanisisa ka lithethefatsi) le lits'ebetso tse sa tsebeng letho (tse hlophisitsoeng litebello, ho qobelloa, ho qobelloa, ho sheba lintho hantle) tse hlahisoang ke ho se sebetse hantle ha potoloho ea striato-thalamo-orbitofrontal.

Ho Utloisisa Matsoalo le Mosebetsi oa Orbitof Pambal Cortex E Nepahetse ho Lemalla

Orbitof Pambal cortex ke sebaka seo se nang le neuronatomicaly se amanang le libaka tsa boko tse tsejoang ho ameha ka litlamorao tse matlafatsang tsa lithethefatsi tsa tlhekefetso. Haholo-holo, li-nucleus li bokellana, tse nkoang e le sona sepheo sa ts'ebetso e matlafatsang ea lithethefatsi tsa tlhekefetso (Koob and Bloom, 1988; Pontieri et al., 1996), merero ho orbitofrontal cortex ka li-nucleodorsal nucleus ea "medialam" Ray le Price, 1993). Ka lehlakoreng le leng, cortex ea orbitofrontal e fana ka lipakanyo tse matla ho li-bokong tsa nucleus (Haber et al., 1995). Cortex ea orbitofrontal e boetse e fumana lipehelo tse tobileng ho tsoa ho lisele tsa DA sebakeng se kenellang hare sa mokokotlo (Oades and Halliday, 1987), e leng khubu ea DA e amanang le litlamorao tsa matlafatso ea lithethefatsi (Koob le Bloom, 1988). Ntle le moo, orbitof Pambal cortex e boetse e amohela lipehelo tse tobileng le tse sa tobang (ka thalamus) tse tsoang libakeng tse ling tsa boko tse tsejoang ka ho ameha ka tšebeliso ea lithethefatsi, joalo ka amygdala, cingates gyrus le hippocampus (Ray le Price, 1993; Carmichael et al., 1995 ). Sena se etsa hore orbitof Pambal cortex e se ke ea ba sepheo se tobileng feela bakeng sa litlamorao tsa lithethefatsi tsa tlhekefetso empa hape le sebaka se ka kopanyang leseli ho tsoa libakeng tse fapaneng tsa maoto le ka lebaka la khokahano ea sona ea ho khutlisetsa tikoloho, sebaka seo ka lehlakoreng le leng se ka fetolang karabelo ea litho tsena tsa maoto. likarolo tsa boko ho tsamaiso ea lithethefatsi (feiga. 1).

Setšoantšo sa 1.

Setšoantšo sa Neuroanatomic sa khokahano ea orbitofrontal cortex e amanang le matlafatso ea lithethefatsi le bokhoba ba tsona. VTA = sebaka sa ho kenella ka mokokotlo, NA = li-bokono, TH = thalamus, OFC = orbitofrontal cortex.

Har'a mesebetsi e fapaneng ea orbitofrontal cortex, karolo ea eona ho boits'oaro bo amanang le moputso e bohlokoa haholo ha e sekaseka ho nka karolo ha eona ho lemalleng lithethefatsi. Ho qala, liphoofolong tsa laboratori ho beoa li-electrode tse hlasimollang ka har'a orbitofrontal cortex habonolo ho etsa hore motho a ikhothatse (Phillips et al., 1979). Litlamorao tsena ho bonahala li fetotsoe ke DA kaha li thibetsoe ke tsamaiso ea bahanyetsi ba li-receptor tsa DA (Phillips et al., 1979). Ho boetse ho amoheloa hantle hore orbitofrontal cortex, ntle le ho sebetsana le tlhaiso-leseling ka thepa e putsoang ea tšusumetso (Aou et al., 1983; Tremblay le Schulz, 1999), le eona e kentse letsoho ho fetoleng boits'oaro ba phoofolo ha litšobotsi tse matlafatsang tsa tsena phetoho ea li-stimuli (Thorpe et al., 1983) le ho mekhatlo ea ho ithuta e matlafatsang (Rolls, 1996; Schoenbaum et al., 1998). Le ha mesebetsi ena e khethiloe bakeng sa batšehetsi ba mmele joalo ka lijo (Aou et al., 1983), ho ka etsahala hore ba be le karolo e ts'oanang bakeng sa batšehetsi ba meriana.

Ka hara liphoofolo liphoofolo tse senyehileng ea "orbital frontal cortex" li baka tšenyo ea ho fetoha hoa mekhatlo ea tšebetso ea matlafatso, 'me li lebisa ho tiisetso le khanyetsong ea ho felisoa hoa boits'oaro bo amanang le moputso (Butter et al., 1963; Johnson, 1971). Sena se re hopotsa se etsahallang batho ba lemaletseng lithethefatsi tseo khafetsa ba reng ha ba qala ho sebelisa moriana ba ke ke ba emisa leha sethethefatsi se se se sa khahlise.

Mosebetsi o mong oa bohlokoa oa tlhahlobo ena ke ho kenella ha orbitofrontal cortex literekeng tse susumetsang (Tucker et al., 1995). Hobane ho lumeloa hore li-circuits tsa striato-cortical li bohlokoa molemong oa likarabo tsa likarabo tse tloaelehileng maemong a sa lekanang (Marsden and Obeso, 1994), ho se sebetse hantle ha sekala sa striato-thalamo-orbitofrontal le ts'ebeliso e mpe ea lithethefatsi se ka nka karolo. ka tšusumetso e matla e sa lokelang ea ho fumana le ho sebelisa sethethefatsi lithutong tse lemaletseng.

Leha ho le joalo, ke lithuto tsa liphoofolo tse fokolang haholo tse entseng lipatlisiso ka kotloloho karolo ea orbitofrontal cortex ho matlafatseng lithethefatsi. Taba ena e koaetsoe ka botlalo libakeng tse ling (Porrino le Lyons, 2000). Mona re batla ho hlokomela hore lithuto tsena li qobella orbitofrontal cortex ka likarabo tse maemong tseo lithethefatsi tsa tlhekefetso li li hlahisang. Mohlala, likhoto tse pepeselitsoeng tikoloho eo ba neng ba kile ba fumana koae ho eona li bonts'a ts'ebetso ea orbitofrontal cortex empa eseng li-nucleus accumbens (Brown et al., 1992). Hape likhoto tse nang le liso tsa orbital frontal cortex ha li bonts'a sebaka se khethiloeng ke cocaine (Isaac et al., 1989). Ka mokhoa o ts'oanang liso tsa thalamic mediodorsal nucleus (ho kenyeletsoa le nucleus ea paraventricular) li bonts'itsoe ho senya boits'oaro bo matlafalitsoeng (Mc Alona et al., 1993; Young le Deutch, 1998) le ho fokotsa taolo ea cocaine (Weissenborn et al., 1998 ). Sena se bohlokoa hobane likarabo tse maemong a bakoang ke lithethefatsi tsa tlhekefetso li kentsoe takatsong e khahliloeng ke batho ka ho pepesehela tšusumetso e amanang le tsamaiso ea lithethefatsi (ke hore khatello ea maikutlo, chelete, lisirinji, seterata) (O'Brien et al., 1998). Karabelo ena ea takatso, le eona ke e 'ngoe ea lisosa tse tlatselletsang ho khutlela ho batho ba sebelisang lithethefatsi hampe (McKay, 1999).

Re boetse re batla ho hlokomela hore ho li-transporter tsa knockout tsa litoeba tsa DA, ho itaola ha k'hok'heine ho hlahisa ts'ebetso ea orbitofrontal cortex (Rocha et al., 1998). Taba ena ea morao-rao e khahla haholo hobane liphoofolong tsena ho ne ho sa amane le ts'ebetso ea ts'ebetso ea li-nucleus bokello, e amoheloang e le sepheo sa ts'ebetso e matlafatsang ea lithethefatsi tsa tlhekefetso. Kahoo thuto ena e fana ka maikutlo a bohlokoa ba orbitofrontal cortex ho boloka tsamaiso ea lithethefatsi tlasa maemo ao matla a bokellanang a senang matla a tumellano a sa sebetseng ka ona.

Le ha e se bakeng sa tšusumetso e amanang le lithethefatsi, lithuto tse inahaneloang lithutong tsa batho li boetse li ntlafalitse karolo ea orbitof Pambal cortex ka boitšoaro bo matla le likarabelo tse maemong a tlase. Mohlala, ts'ebetso ea orbitofrontal cortex lithutong tsa batho e tlalehiloe ha ts'ebetso ea ts'ebetso ea kelello e amahanngoa le moputso oa chelete empa eseng ha e se (Thut et al., 1997), hape le ha u lebelletse ts'usumetso e nang le maemo (Hugdahl et al., 1995).

Orbitof Pambal Cortex Pathology lithutong tsa Batho

Ho batho, maloetse a orbitofrontal cortex le striatum a tlalehiloe ho bakuli ba nang le mathata a feteletseng a tlatselletsang (Baxter et al., 1987; Modell et al., 1989; Insel, 1992), e arolelanang le bokhoba boleng ba boitšoaro bo qobelloang. Ho feta moo, ho bakuli ba nang le lefu la Tourette, litakatso, ho qobelloa le ho hloka maikutlo, tseo kaofela e leng boits'oaro bo teng ts'ebetsong ea lithethefatsi, li fumanoe li amahanngoa le keketseho ea ts'ebetso ea metabolic ho orbitofrontal cortex le striatum (Braun et al., 1995). Hape tlaleho ea nyeoe ea morao-rao mabapi le mokuli ea nang le leqeba la methapo ea orbitofrontal cortex e hlalosa lefu la ho alima koloi ka mokhoa o qobelloang o lebisang ho ts'oaroeng khafetsa le ho hlalosoang ke taba eo e le phomolo e khahlisang (Cohen et al., 1999).

Ho khahloa ke tlhahlobo ena hape ho na le litlaleho tse susumetsang thalamus ka boits'oaro bo qobelloang. Ho hlokomelehang ke lithuto tsa tleliniki ea bongaka tse hlalosang boithati bo khothalletsang ho bakuli ba nang le li-electrodes tse susumetsang tse kentsoeng thalamus (Schmidt et al., 1981; Portenoy et al., 1986). Boitšoaro bo phehellang ho bakuli bana bo hlalositsoe e le boikhopotso ba boits'oaro bo qobelloang ba lithethefatsi bo bonoang lithutong tse lemaletseng.

Lithuto tsa ho etsa litšoantšo ka boloi ba lithethefatsi

Boholo ba lithuto tse inahaneloang tse amanang le bokhoba ba tahi li sebelisitse positron emission tomography (PET) hammoho le 2deoxy-2- [18F] fluoro-d-glucose, analog ea glucose, ho lekanya metabolism ea "glucose" ea tikoloho. Hobane metabolism ea "glucose metabolism" e sebetsa e le sesupo sa ts'ebetso ea boko, leano lena le lumella 'mapa oa likarolo tsa boko tse fetohang e le ts'ebetso ea ts'ebetso ea lithethefatsi kapa ho tlosoa hoa lithethefatsi mme o nolofalletsa ho tsebahala ha mangolo afe kapa afe lipakeng tsa liphetoho tšebetsong ea boko ba tikoloho le matšoao ho basebelisi ba lithethefatsi. . Leha ho le joalo, lipheo tse fapaneng tsa limolek'hule tse amehang ho li-neurotransmission tsa DA le tsa li-neurotransmitters tse ling, tse kang li-receptors, baeti le li-enzyme, le tsona li fumanoe lipatlisiso. Tekanyetso e tlase haholo ea mahlaseli a tsoang ho li-positron emitters e lumelletse tekanyo ea litefiso tse fetang e le 'ngoe tsa limolek'hule nthong e itseng.

Ho Ithuta ka Litaba tsa ho Lemalla Cocaine

Ketsahalo ea Orbitof Pambal Cortex nakong ea Detoxification

Boithuto bo lekolang liphetoho ka linako tse fapaneng kamora hore detoxation e etsoe ho batho ba hlekefetsang koae le lithethefatsi tsa joala. Tabeng ea batho ba hlekefetsang k'hok'heine, lithuto tsena li bonts'itse hore nakong ea ho khaola pele (ka nako ea beke e le 1 ea ts'ebeliso ea koae) metabolism ho orbitofrontal cortex le striatum e ne e phahame haholo ho feta maemong a taolo (Volkow et al., 1991). The metabolism ho orbitofrontal cortex e ne e amana haholo le botebo ba ho lakatsa; Ha metabolism e le matla le ho feta, ke eona e batlang e le matla le ho feta.

Ho fapana le moo, ba hlekefetsang koae ka "cocaine" ba ithutileng eona nakong ea ha ba ne ba tlohela lintho tse ngata, ba ile ba fokotsa khafetsa libakeng tse 'maloa tse ka pele, ho kenyelletsa orbitofrontal cortex le anterior cingulate gyrus, ha ba bapisoa le taolo e sa hlekefetsang (Volkow et al., 1992). Lits'ireletso tsena li ile tsa phehella leha lithuto li ne li lekoa hape likhoeli tse 3-4 kamora nako ea pele ea ho khutla.

Dopamine le Ketsahalo ea Orbitofrontal Cortex

Ho etsa liteko haeba ho e-na le pherekano mesebetsing ea orbitofrontal cortex le anterior cingrate gyrus ho batho ba hlekefetsang koae ka lebaka la diphetoho tse bakoang ke liphetoho tsa tšebetso ea boko ba DA, re ile ra hlahloba kamano lipakeng tsa liphetoho lipolotong tsa DA D2 le liphetoho tsa metabolism ea tikoloho. Ha ho bapisoa le taolo, batho ba hlekefetsang koae ka koae (nakong ea khoeli e le 'ngoe ea ts'ebeliso ea koae ea ho qetela) ba bontšitse maemo a tlase a DA D1 ho striatum mme phokotso ena e ile ea phehella likhoeli tse 2 - 3 kamora ho ts'oaroa. Phokotso ea litheko tsa li-receptor tsa D4 tsa striatal li ne li amahanngoa le metabolism e fokotsehileng ho cortex ea orbitofrontal le gterus ea ka ntle ea bongoaneng (Volkow et al., 2a). Lintho tse nang le likarolo tse tlase haholo tsa li-receptor tsa D1993 li bonts'itse boleng bo tlase ba metabolic libakeng tsena tsa boko (sa feiga 2).

Setšoantšo sa 2.

Kamano lipakeng tsa metabolism ea tsoekere ea boko ba tikoloho ho cingulate gyrus (r = 0.64, df 24, P <0.0005) le orbitofrontal cortex (r = 0.71, df 24, P <0.0001) le ho fumaneha ha dopamine D2 receptor (Ratio Index) ho striatum e tlositsoeng batho ba hlekefetsang koae.

Mokhatlo oa metabolism ho orbitofrontal cortex le cingates gyrus e nang le li-receptor tsa DA D2 o ile oa hlalosoa o bonts'a molao o sa laoloang ke DA oa libaka tsena ka projeke-thalamo-cortical merero (Nauta, 1979; Heimer et al., 1985; Haber, 1986) kapa melaoana ea methapo ea methapo ea methapo ea DA D2 ka li-cortico-striatal path (Le Moal le Simon, 1991). Nyeoe ea pele e ka bolela sekoli se ka sehloohong tseleng ea DA empa sa morao se ka bolela sekoli se kahara mokokotlo oa orbitofrontal le cingate gyrus ho ba hlekefetsang koae.

Hobane phokotso ea metabolism ho orbitofrontal cortex le cingrate gyrus ho batho ba hlekefetsang koae e ne e amana le maemo a D2 a receptor ho ne ho ka ba le thahasello ea ho lekola hore na ts'ebetso ea DA e eketsehang e ka khutlisa liphetoho tsena tsa metabolic. Bakeng sa sepheo sena ho ile ha etsoa lipatlisiso tse ileng tsa lekola litlamorao tsa keketseho ea DA (e fumanoang ke tsamaiso ea psychostimulant drug methylphenidate) ho metabolism ea "glucose metabolism" ea ts'ebeliso ea tlhekefetso ea cocaine. Methylphenidate (MP) e eketsehile metabolism ka gypus ea anterior, thalamus e nepahetseng le cerebellum. Ntle le moo, ho batho ba hlekefetsang koae eo litho tsa eona tsa MP li ileng tsa etsa hore litakatso tsa bona li be le litakatso tse matla (empa eseng ho bao e neng e sa ba etse) MP e ile ea eketsa metabolism ka koteng e nepahetseng kapa e nepahetseng ea sebopeho sa methapo (Fig. 3).

Setšoantšo sa 3.

Litšoantšo tsa metabolism tsa bokong tsa tikoloho tsa motho ea sebelisang koae hampe eo methylphenidate e ileng ea mo hohela ka takatso e matla le eo a sa kang a e etsa. Hlokomela ts'ebetso ea "cortex" e nepahetseng ea orbitofrontal (R OFC) le ea setamen se nepahetseng (R PUT) ka taba e tlalehang takatso e matla.

Keketseho ea ts'ebetso ea metabolic ho cingate gyrus kamora tsamaiso ea MP e fana ka maikutlo a hore hypometabolism ea eona ho ba hlekefetsang koae e bonts'a karolo e ileng ea fokotsa ts'ebetso ea DA. Ho fapana le hoo, MP e ile ea eketsa metabolism ho cortex ea orbitofrontal lithutong tseo e ntlafalitseng takatso ea eona. Sena se ka fana ka maikutlo a hore ts'ebetso ea hypometabolic ea orbitofrontal cortex ho basesisi ba koae ba detoxified e ka 'na ea kenyelletsa ho senyeha ha li-neurotransmitters tse ling ntle le DA (ke hore glutamate, serotonin, GABA). Sena se ka boela sa fana ka maikutlo a hore leha ntlafatso ea DA e kanna ea hlokahala ha e ea lekana ka bo eona ho kenya tšebetsong cortex ea orbitofrontal.

Kaha cortex ea orbitofrontal e ameha ka pono ea ho se tsitsinyehe ha matlafatso, ts'usumetso e pharalletseng ea cortex ea orbitofrontal lithutong tse tlalehileng takatso e matla e ka bonts'a ho nka karolo ha eona e le ts'ebetso ea liphetho tse matlafatsang tsa MP. Leha ho le joalo, hobane ts'ebetso ea orbitof Pambal cortex e boetse e amana le tebello ea ts'usumetso (Hugdahl et al., 1995), ts'ebetso ea eona lithutong tseo Mopalamente a ileng a susumetsa takatso ea hae e ka bonts'a tebello lithutong tsena tsa ho amohela tekanyetso e 'ngoe ea MP. Ho feta moo, ts'ebetso ea potoloho e tšoaeang moputso o lebelletsoeng e kanna ea lemohuoa e le ho lakatsa. Hore khokahano le takatso ea takatso e boetse e bonoe ho striatum e ka bonts'a khokahano ea eona e kopanetsoeng le "cortex" ea orbitofrontal ka potoloho ea striato-thalamoorbitofrontal (Johnson et al., 1968).

Ts'ebetso ea cortex ea orbitofrontal ke MP, sethethefatsi sa lithethefatsi se tšoanang le cocaine (Volkow et al., 1995), e ka ba e 'ngoe ea mekhoa eo ka eona cocaine e lakatsang takatso le taolo e latelang ea khatello ea lithethefatsi nthong e lemaletseng.

Orortofrontal Cortex le takatso ea Cocaine

Hyperacaction ea orbitofrontal cortex ho bonahala e amana le litlaleho tsa boithati tsa takatso ea koae. Sena se hlokometsoe, joalo ka ha ho hlalositsoe likarolong tse fetileng, ho batho ba hlekefetsang koae ba ile ba lekoa nakoana kamora ts'ebeliso ea ho qetela ea koae le ha tsamaiso ea MP e ile ea fella ka keketseho ea takatso ea bona.

Ts'ebetso ea cortex ea orbitofrontal e boetse e bontšitsoe lithutong tse neng li etselitsoe ho lekola libaka tsa boko tse ileng tsa qala ho sebetsa nakong ea ho pepesehela ts'usumetso e reretsoeng ho tsosa takatso ea cocaine. Bakeng sa thuto e le 'ngoe ea litakatso tsa koae e ile ea hlahisoa ke puisano ea sehlooho sa koae (ho itukisetsa cocaine bakeng sa ho itaola). Metabolism ea "glucose metabolism" ea 'mele nakong ea puisano ka sehlooho sa cocaine e ile ea bapisoa le seo nakong ea puisano ea sehlooho se sa nke lehlakore (genogram ea lelapa). Puisano ea sehlooho sa cocaine e ile ea eketsa metabolism haholo ho orbitofrontal cortex mme ea siea insort cortex ha e bapisoa le tlhahlobo ea sehlooho ea sehlooho (Wang et al., 1999). Ho eketseha ha metabolism ea orbitofrontal cortex ho kenyelletsa ts'ebetso ho amygdala, preortal cortex le cerebellum ho boetse ho tlalehiloe thutong e sebelisang videotape ea litšoantšo tsa cocaine tse etselitsoeng ho tsosa takatso ea (Grant et al., 1996).

Leha ho le joalo, phuputso e ileng ea lekanya liphetoho lipakeng tsa phallo ea mali a likhoerekhoere (CBF) ha a araba videotape ea cocaine e tlalehiloe ts'ebetso ea gingus ea gingus le amygdala empa eseng ea orbitofrontal cortex nakong ea litakatso (Childress et al., 1999). Lebaka la ho se khone ho bona ts'ebetso ea cortex ea orbitof Pambal ha le hlake.

Ho hlohlelletsa lithethefatsi tsa Dopamine, takatso ea Thalamus le Cocaine

Liphetoho likhatellong tsa DA bokong ba motho li ka lekoa ka PET e sebelisa [11C] raclopride, ligand eo ho tlamelloa ho eona D2 receptor e amehang tlholisano le endo native DA (Ross le Jackson, 1989; Seman et al., 1989; Dewey et al., 1992). Sena se etsoa ka ho lekanya liphetoho tse tlamang tlamiso ea [11C] raclopride e hlahisitsoeng ke ho kenella hoa meriana (ke hore MP, amphetamine, cocaine). Hobane [11C] raclopride binding e na le bokhoni bo boholo ba ho hlahisa (Nordstrom et al., 1992; Volkow et al., 1993b) liphokotso tsena li supa liphetoho lipolotiking ho karabelo ea DA. Hlokomela hore boemong ba MP, bo eketsang DA ka ho thibela morekisi oa DA (Ferris et al., 1972), liphetoho tse ho DA ha se mosebetsi oa maemo feela oa transporter blockade empa hape le palo ea DA e lokollotsoeng. . Haeba maemo a tšoanang a li-transporter blockade tsa DA a thehiloe ho lihlopha tse peli tsa lithuto, liphapang tsa ho tlamisoa ha [11C] raclopride boholo ba tsona li bakoa ke liphapang tsa ho lokolloa ha DA. U sebelisa leano lena ho bontšitsoe hore ka botsofaling ho na le phokotseho ea tokollo ea DA lithutong tse phetseng hantle tsa batho (Volkow et al., 1994).

Ho bapisoa le likarabo ho MP lipakeng tsa banyetsi ba tlhekefetso le taolo ea cocaine ho bonts'itse hore litheko tsa MP- e kenyellelitseng lintlafatso ho [11C] raclopride binding ho striatum ho bahlaseli ba koae e ne e le ka tlase ho halofo ea tse bonoang ho li-taolo (Volkow et al., 1997a). Ho fapana le hoo, ho batho ba hlekefetsang koae ka koae, empa eseng maemong a taolo, MP e fokotsehile haholo tlamo ea [11C] raclopride ho thalamus (sa feiga. 4a). MP-indedu e fokotseha ho [11C] raclopride binding thalamus, empa eseng ho striatum, e ne e amahanngoa le keketseho ea MP ea ho khothaletsa litlaleho tsa boithati tsa ho lakatsa (Fig. 4b). Sena se ne se khahla ho tloha ha DA e boloka taba ea thalamus e lekanyelitsoe feela ho li-nucleodorsal le paraventricular nuclei, tse romelloang li-nerbit ho orbitofrontal cortex le cingulate gyrus ka tatellano (Groenewegen, 1988), mme kaha ho na le bohlokoa ba koae le cocaine le MP ho thalamus (Wang et al., 1993; Madras le Kaufman, 1994). Ho ne ho boetse ho tsoteha hore lits'ebetso tse tloaelehileng li ne li sa bonts'e karabo ho thalamus, eo haeba ho na le letho le neng le ka supa tseleng ea DA e ntlafalitsoeng e sa tloaelehang lithutong tse lemaletseng. Kahoo, motho a ka hakanya hore ts'ebetsong e lemalloang ea ts'ebetso e lemalloang ea DA thalamic pathway (e ka 'nang eaba li-pakati tsa methapo ea methapo) e ka ba e' ngoe ea mekhoa e lumellang ts'ebetso ea orbitofrontal cortex.

Setšoantšo sa 4.

(A) Litlamorao tsa methylphenidate (MP) mabapi le ho tlama [11C] raclopride ho thalamus (Bmax / Kd) ho li-control le ho batho ba hlekefetsang k'hok'heine. (B) Kamano lipakeng tsa liphetoho tse bakiloeng ke MP ho Bmax / Kd ho thalamus le liphetoho tse susumetsoang ke MP litlalehong tsa boithati tsa takatso ea batho ba hlekefetsang cocaine (r = 61, df, 19, P <0.005).

Kakaretso ea Boithuto ba ho Qhekella ho Batho ba Hlekefetsang Cocaine

Liphuputso tse entsoeng ka boqhetseke li fane ka bopaki ba tlhekefetso ho striatum, thalamus le orbitofrontal cortex ho batho ba hlekefetsang koae. Boemong ba striatum, ba hlekefetsang cocaine ba bonts'a ho fokotseha hoa maemo a li-receptor tsa DA D2 hammoho le tokollo e sa hlatheng koana le koana ea DA. Ka thalamus, ba hlekefetsang cocaine ba bonts'a karabelo e ntlafalitsoeng ea tsela ea DA ea thalamic. Ka orbitofrontal cortex, ba hlekefetsang cocaine ba bonts'a khatello ea kelello nakoana kamora ts'ebeliso ea ho qetela ea koae hape le nakong ea liteko tse hohelang litakatso tsa lithethefatsi le hypoacaction nakong ea ho khaotsa, e amanang le phokotso ho li-receptor tsa DA D2. Re hakanya hore phokotso e matla ea tokollo ea DA le li-receptor tsa DA D2 li fella ka ho fokotseha hoa ts'ebetso ea lipotoloho tse lebisang ho hypoacaction ea cingates gyrus mme li ka kenya letsoho ho cortex ea orbitofrontal.

Ho Ithuta ka Litaba tsa Joala

Ketsahalo ea Orbitof Pambal Cortex nakong ea Detoxification

Liphuputso tse ngata li entsoe ho lekola liphetoho tsa metabolism lithutong tsa joala nakong ea ts'ehetso. Boholo ba lithuto li lula li bonts'a phokotso ea metabolism e ka pele, ho kenyeletsoa le anterior cingate gyrus le orbitofrontal cortex, lithutong tsa joala. Leha liphuputso li bonts'itse pholiso e kholo mehatong ea mantlha ea metabolism le ts'oaetso ea joala, ha e bapisoa le taolo, lino tse tahang li ntse li na le metabolism e tlase haholo ho orbitofrontal cortex le ho anterior cingulate gyrus (Volkow et al., 1997b). Ka mokhoa o ts'oanang lithuto tse entsoeng ka mokelikeli o le mong oa photon emission computed tomography li bonts'itse phokotso e kholo ho CBF ho orbitofrontal cortex lithutong tsa joala nakong ea detoxification (Catafau et al., 1999). Taba ea hore liphetoho tsa orbitofrontal cortex li ne li le teng kamora likhoeli tse 2-3 kamora ho tlosa 'mele (Volkow et al., 1997b) e bonts'a hore ha se mosebetsi oa ho tlohela joala empa e emela liphetoho tse tšoarellang nako e telele. Ntle le moo, taba ea hore likhoto li pheta botahoa le joala e lebisa ho senyeha ha methapo ea kutlo ea orbital frontal cortex (Corso et al., 1998) e hlahisa monyetla oa hore hypometabolism e phehellang ka orbitofrontal cortex ho lino tse tahang e ka bonts'a litlamorao tsa joala ba joala.

Dopamine le Ts'ebetso ea Orbitofrontal Cortex

Tšitiso ea "striato-thalamo-orbitofrontal" e boetse e khothalletsoe ho nka karolo ho lakatseng le tahlehelo ea taolo taolong ea joala (Modell et al., 1990). Ha lithuto tsa PET li tlaleha phokotso ea bohlokoa ho li-receptor tsa D2 ho lino tse tahang ha li bapisoa le taolo (Volkow et al., 1996b), ha ho na lipatlisiso tse entsoeng ho tseba hore na ho na le kamano pakeng tsa litheko ho li-receptor tsa D2 le liphetoho mesebetsing ea metabolic. ka orbitofrontal cortex litabeng tsa joala.

Le ha DA e tšoanela litlamorao tse matlafatsang tsa joala (El-Ghundi et al., 1998), litlamorao tsa eona ho li-neurotransmitters tse ling (opiates, NMDA, serotonin, GABA) le tsona li bile le tšusumetso ho matlafatsong ea eona ea ho matlafatsa le ho lemalla (Lewis, 1996) ).

GABA le Ts'ebetso ea Orbitof Pambal Cortex

Kameho ea joala ho gaba neurotransication e khahla haholo hobane litekong tse hlekefelitsoeng ke batho, joala bo thusa ho tsamaisa methapo ea kutlo ea Gaba. Ho boetse ho nahanoa ka hore ts'oaetso ea joala ke litlamorao tsa ts'ebetso ea ts'ebetso ea boko ba GABA (Coffman le Petty, 1985). Leha ho le joalo, ha ho tsejoe hantle hore na liphetoho tsa tšebetso ea boko ba GABA li ka kenya letsoho joang boits'oaro bo lematsang lithutong tsa joala. PET e sebelisitsoe ho ithuta sistimi ea boko GABA ka ho lekanya liphetoho tsa metabolic bokong tse hlahisoang ke phephetso e matla le lithethefatsi tsa benzodiazepine - sathe benzodiazepines, joalo ka joala, e boetse e nolofalletsa methapo ea methapo ea kutlo ea GABA bokong (Hunt, 1983) - le ka ho lekanya ka kotloloho mahloriso a li-receptor tsa benzodiazepine bokong ba motho.

Karabelo ea metabolic ea boko ea mantlha ho loreazepam lithutong tse tahiloeng tsa joala e sa tsoa bapisoa le e ka taolo e phetseng hantle. Lorazepan e theola metabolism ea "glucose" eohle ka mokhoa o tšoanang lithutong tse tloaelehileng le tsa joala (Volkow et al., 1993c). Leha ho le joalo, lithuto tsa lino tse tahang li bontšitse karabo e fokolang haholo ho feta taolo ho thalamus, striatum le orbitofrontal cortex. Liphumano tsena li ile tsa hlalosoa e le ho bonts'a kutloisiso e fokotsehileng ea ts'ebetso ea methapo ea kutlo ea mokokotlo mokokotlong oa striato-thalamo-orbitofrontal ka har'a lino tse tahang nakong ea kotlo ea pele ho nako (libeke tse 2 ho 4 kamora ts'ebeliso ea lino tse tahang). Phuputso e ileng ea latela e ile ea lekola boholo ba likarabo tsena tse sa nepahalang ha li bapisoa le tlhaiso-pele ea nako. Boithuto bona bo bonts'itse hore le ka mora detoxation ea nako e telele (libeke tse 8 ho isa ho tse ling kamora ho khaotsoa) lino tse tahang li bile le karabelo e sa hlakang kahara orbitofrontal cortex ha li bapisoa le taolo (Volkow et al., 10b). Sena se fana ka maikutlo a hore hyporesponsivity ea orbitofrontal cortex ha se ts'ebetso ea ho itlopa joala feela empa e ka supa ho fokotseha ho khethehileng hoa kutloisiso ea kutlo ho thibelo ea methapo ea kutlo ho lino tse tahang.

Bopaki bo bong ba ho nka karolo ha GABA liphetohong tse sa feleng tsa ts'ebetso ho orbitofrontal cortex ea lino tse tahang bo boetse bo fanoa ke phuputso e lekanyang maemo a li-receptor tsa benzodiazepine bokong ba batho ba tahang joala (> likhoeli tse 3 tsa ho tlosa 'mele) ba sebelisa [123I] Iomazenil. Phuputso ena e bontšitse hore lino tse tahang tse nang le ts'oaetso li na le phokotso e kholo maemong a li-benzodiazepine receptors ho orbitofrontal cortex ha e bapisoa le litsamaiso (Lingford-Hughes et al., 1998). Ho fokotseha ha maemo a li-benzodiazepine receptors sebakeng sa orbitofrontal cortex ho ka hlalosa likarabo tse sa hlakang tsa methapo ea methapo tsamaisong ea lorazepam sebakeng sena sa boko lithutong tsa joala. Motho a ka beha lebaka la hore phokotso ea kutlo ho GABA methapo ea kutlo e ka ba phoso molemong oa matšoao a thibelang ho emisa ts'ebetso ea orbitofrontal cortex lithutong tsena.

Serotonin le Ts'ebetso ea Orbitofrontal Cortex

Cortex ea orbitof Pambal e fumana serotonergic innervation ea bohlokoa (Dringenberg le Vanderwolf, 1997) ka hona, tlhekefetso ea serotonin le eona e ka kenya letsoho ts'ebetsong e sa tloaelehang ea sebaka sena sa boko. Bopaki ba hore sena e kanna ea ba se fanoa ke phuputso e ileng ea lekanya liphetoho tsa metabolism ea boko ea tikolohong ho arabela m-chlorophenylpiperazine (mCPP), sethethefatsi se kopaneng sa serotonin agonist / antagonist, literekeng tsa tahi le taolo. Boithuto bona bo bonts'itse hore ts'usumetso e susumetsoang ke mCPP ho thalamus, orbitofrontal cortex, caudate le frontal ea bohareng e ile ea phatloha haholo ho lino tse tahang ha li bapisoa le taolo (Hommer et al., 1997). Sena se ne se hlalosoa se bonts'a potoloho e kholo ea lingaka tsa joala. Karabelo e sa tloaelehang ho mCPP e bonts'a ho kenya letsoho ha tsamaiso ea serotonin litsietsing tse bonoang potolohong ena ho bakuli ba joala. Ho ts'ehetsa sena ke boithuto bo bonts'ang liphokotso ho baeti ba serotonin, ba sebeletsang e le matšoao bakeng sa lits'a tsa serotonin, mesencephalon ea lithuto tsa joala (Heinz et al., 1998). Mabapi le taba ena ebile ho a khahlisa ho tseba hore lithethefatsi tsa serotonin reuptake inhibitor li bontšitsoe li sebetsa ho fokotsa tšebeliso ea joala lithutong tsa joala (Balldin et al., 1994).

Kakaretso ea Lipapatso tsa Imaging ka Alcoholics

Lithuto tse entsoeng ka ho ts'oara li fane ka bopaki ba tlhekefetso ho striatum, thalamus le orbitofrontal cortex ho lino tse tahang. Ts'ebetsong ea "striatum, thalamus" kapa "orbitofrontal cortex" e na le karabo ea "metabolism" ea "" "metabolism kapa" gabaergic "kapa" serotonergic ". Ntle le moo, lino tse tahang tse tsoang ka ntle ho detoxified li boetse li bonts'a ho fokotseha ha metabolism, phallo le li-receptor tsa benzodiazepine ho orbitof Pambal cortex. Tsena tlhekefetso ka hona e kanna ea bonts'a liphetoho tsa karolo ea GABAergic le serotonergic.

Tlhahiso ea lithethefatsi e le bokuli ba drive le boits'oaro bo ho qobella

Mona re beha lebaka la ho pepesehela lithethefatsi tsa tlhekefetso ho sitisa ts'ebetso ea potoloho ea striato-thalamo-orbitofrontal. Ka lebaka la ts'ebetso ena karabelo e nang le boemo e ba teng ha taba e lemalloang e pepesitsoe lithethefatsing le / kapa tse amanang le lithethefatsi tse etsang hore potoloho ena e be le ts'ebetso e kholo ea ho fumana moriana ona (o lemohuoa ka letsoalo le letle) hape tsamaiso ea sethethefatsi (se lemohuoeng ka hloko e le tahlehelo ea taolo). Mokhoa ona oa ho lemalla o lematsa hore maikutlo a susumetsoang ke lithethefatsi ke a bohlokoa haholo mohato oa pele oa ho itaola lithethefatsi empa ka boiketlo bo sa feleng ba ts'ebetso e ke ke ea baka tšebeliso e tlamang ea lithethefatsi. Ho fapana le moo, ho se sebetse hantle ha potoloho ea striatothalamo-orbitofrontal, eo ho tsejoang hore e ameha ka boits'oaro bo mamellehang, e fana ka tlaleho ea ts'ebeliso e tlamang. Re beha lebaka la hore karabelo e khahlisang e hlokahala ho theha mokhatlo o hlophisitsoeng o nang le lithethefatsi bakeng sa ts'ebetso ea ho hlahisa ts'ebetso ea orbitofrontal cortex ka mor'a ho hlahella. Cortex ea orbitofrontal, ha e se e hlahisitsoe, e tla etsa hore se nkoang e le takatso e matla kapa khokahano ea ho sebelisa moriana leha sehlooho se ka ba le lipontšo tse hanyetsanang tsa kelello tse mo joetsang hore a se ke a se etsa. Hang ha a nka sethethefatsi ts'ebetso ea DA e sebetsang nakong ea tahi e boloka ts'ebetso ea potoloho ea striato-thalamo-orbitof pelaal, e behang mohlala oa ts'ebetso o hlahisang tiisetso ea boits'oaro (taolo ea lithethefatsi) mme e amoheloang ka hloko e le tahlehelo ea taolo.

Papiso e ka bang molemo ho hlalosa ho arohana ha thabo ka lebaka la ts'ebeliso ea lithethefatsi lithutong tse lemaletseng e ka ba ntho e etsahalang nakong ea ho hloka lijo nako e telele ha thuto e tla ja lijo life kapa life ntle le tatso ea eona, esita leha e nyonyeha. Tlas'a maemo ana takatso ea ho ja ha e khanneloe ke thabo ea lijo empa e susumetsoa ke takatso e matla ea tlala. Ka hona ho ka bonahala eka nakong ea ts'oaetso taolo ea lithethefatsi e sa foleng e hlahisitse liphetoho tsa boko tse nkoang e le boemo ba ho potlaka bo sa lumellane le tse boletsoeng metseng ea lijo tse matla kapa ho haella ha metsi. Leha ho le joalo, e fapane le boemo ba 'mele bo potlakileng boo ts'ebetso ea ts'ebetso e tla etsa hore boemo bo felisoe le ho emisoa hoa boitšoaro, maemong a lemalloang ke pherekano ea cortex ea orbitofrontal hammoho le keketseho ea DA e phahamisitsoeng ke tsamaiso ea sethethefatsi se thehile mohlala oa tšebeliso e matla ea lithethefatsi e sa felisoeng ke takatso le / kapa tlholisano.

Nakong ea ho khaola le ntle le ts'usumetso ea lithethefatsi, potoloho ea striato-thalamo-orbitofrontal e fetoha hypofunctional, e lebisang ho fokotsoe ha drive bakeng sa boits'oaro bo susumetsoang ke sepheo. Mokhoa oa phetoho e teng tšebetsong potolohong ena, e ferekanyang kelello ha ho se na lithethefatsi kapa / kapa tse susumetsang tse amanang le lithethefatsi le khatello ea maikutlo nakong ea tahi, e ts'oana le keketseho e bonoang ka lefu la sethoathoa, e bonts'ang keketseho ea ketsahalo ea ntho e sa tloaelehang nakong ea ho kula. nako ea ictal le ka ketsahalo e fokotsehileng nakong ea lipakeng (Saha et al., 1994). Ts'ebetso e tšoarellang nako e telele ho orbitofrontal cortex e ka lebisa motho ho bolela esale pele hore ts'ebetso ea ts'ebeliso e mpe ea lithethefatsi e ka ba teng le kamora nako e telele ea ho tlohela lithethefatsi ka lebaka la ts'ebetso ea meputso e mengata (nucleus accumbens, amygdala) ka ho pepesehela lithethefatsi kapa lithethefatsi. ho susumetsoa ke maemo a lithethefatsi. Ha e le hantle liphuputso tse fumanoang liphoofolong tsa mahlale li bonts'itse ho khutlisetsoa hoa ts'ebeliso ea lithethefatsi ka mor'a ho tlohela lithethefatsi ka mor'a ho pepesetsoa sethethefatsi (Ahmed le Koob, 1998).

Potso e khahlisang e hlahisoang ke mohlala ona ke boholo ba tlhekefetso e kahara cortex ea orbitofrontal e tobileng le litšitiso tse amanang le tšebeliso ea lithethefatsi kapa hore na li baka boitšoaro bo mang bo hatelletsang. Leha ho se na data e ngata mabapi le ho ata ha boits'oaro bo bong bo hatelletsoeng lithutong tse lemalloang, ho na le bopaki bo tsoang lipatlisong tseo bahlorisi ba lithethefatsi ba tlalehang ba nang le likalo tse phahameng ho likala tse qobelloang tsa botho bo fetisisang ho batho ba sa sebeliseng lithethefatsi hampe (Yeager et al., 1992). Ho feta moo lithuto li bonts'itse hore papaling ea papali ea methapo ea kutlo, e leng bothata bo bong ba boitšoaro bo qobelloang, ho na le setsoalle le joala bo phahameng le / kapa tšebeliso e mpe ea lithethefatsi (Ramirez et al., 1983).

Mofuta ona oa bokhoba ba tahi o na le litlamorao tsa kalafo hobane o ka fana ka maikutlo a hore lithethefatsi tse ka fokotsang monyako oa ts'ebetso ea tsona kapa tsa eketsa monyako oa thibelo ea tsona li ka ba molemo molemong oa kalafo. Ntlheng ena hoa khahlisa hore sethethefatsi sa anticonvulsant gamma vinyl GABA (GVG), se fokotsang thabo ea methapo ea kutlo ka ho eketsa mohopolo oa GABA bokong, se bonts'itsoe se sebetsa ho thibela boits'oaro ba lithethefatsi le ho beha likhetho ho sa natsoe lithethefatsi tsa tlhekefetso (Dewey et al., 1998, 1999). Le ha bokhoni ba GVG ba ho thibela keketseho e bakoang ke lithethefatsi ho DA ho li-nucleus accumbens ho boletsoe hore e tla ikarabella bakeng sa ts'ebetso ea eona ea ho thibela maemo a khethiloeng le ho itaola, mona re supa hore bokhoni ba GVG ba ho fokotsa thabo ea methapo ea kutlo le bona bo ka ameha. ka tšitiso ea eona ea ts'ebetso ea potoloho ea striato-thalamo-orbitofrontal. Hape, hobane potoloho ea striato-thalamo-orbitofrontal e laoloa ke li-neurotransmitters tse ngata (Modell et al., 1990), lithethefatsi tse seng tsa dopaminergic tse fetolang tsela ena le tsona li ka ba molemo ho phekoleng bokhoba ba lithethefatsi. Ntlheng ena hoa khahlisa ho hlokomela hore lithethefatsi tse eketsang mohopolo oa serotonin bokong li fokotsa ts'ebetsong ea cocaine (Glowa et al., 1997) athe lits'ebetso tse fokotsang serotonin li eketsa lintlha tse tlolang taolo ea koae (Loh le Roberts, 1990), a ho fumana e neng e hlalosoa e le serotonin e sitisang ts'ebetso ea ho itaola ka lithethefatsi.

Leha lithuto tsa ho nahana ka monahano li bonahala li tlatselletsa potoloho ea litheko tsa lithethefatsi, likarolo tse ling tsa boko, tse kang anterior cingulate gyrus, medial temporal organ (amygdala le hippocampus) le insort cortex, le tsona li bonahala li ameha. Le ha lithuto tsa ho nahana li hlahisitse orbitofrontal cortex ka ho lemalla, lipatlisiso tse eketsehileng lia hlokahala ho khetholla libaka tse kahare ho orbitof Pambal cortex le thalamus tse amehang.

Notes

Patlisiso ena e ne e tšehelitsoe ke karolo ea Lefapha la Matla a Amerika (Ofisi ea Bophelo le Patlisiso ea Tikoloho) tlasa Konteraka DE-ACO2-98CH10886, Institute of Drug Abuse under Grant no. DA 06891 le Setsi sa Ts'ebeliso e Mpe ea Joala le Joala tlasa Grant no. AA 09481.

Lengolo la aterese ho Nora D. Volkow, MD, Lefapha la Bongaka, Bldg 490, Upton, NY 11973, USA. Email: [imeile e sirelelitsoe]

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