Ho fokotseha ho hoholo ha ho lokolloa ha Dopamine ka Striatum Lijong tse tahiloeng tse sa tsitsitseng: Ho kenyeletsoa ha Orbitofrontal (2007) e ka khoneha

J Neurosci. 2007 Nov 14;27(46):12700-6.

Volkow ND, Wang GJ, Telang F, JS Fowler, Logan J, Jayne M, Ma Y, Pradhan K, Wong C.

mohloli o moholo

Setsi sa Naha sa Tlhekefetso ea Lithethefatsi, Bethesda, Maryland 20892, USA. [imeile e sirelelitsoe]

inahaneloang

Boleng ba moputso (meputso ea tlhaho le lithethefatsi) bo amahanngoa le ho eketseha ha dopamine ka har'a li-nucleus tse bokellaneng mme li fapana joalo ka mosebetsi oa maemo. Cortex ea pele-pele e kentsoe molemong oa ho itšetleha ka moputso le ho boleng bo phahameng bo ntlafalitsoeng boo lithethefatsi li nang le tšebeliso ea lithethefatsi, leha mekhoa e sa utloisisoe hantle. Mona re leka hypothesis ea hore cortex ea pele e laola boleng ba meputso ka ho fetolela keketseho ea dopamine ka li-bokellase tsa nucleus le hore molao ona o sitisoa ho lithuto tse lemalloang.

Re sebelisitse positron emission tomography ho lekola mosebetsi oa preortal cortex (ho lekanya metabolism ea glucose ea kelello le [18F] fluorodeoxyglucose) le keketseho ea dopamine (e lekantsoe le [11C] moralo, D2/D3 receptor ligand e nang le binding e amehang ho endo native dopamine) e khothalletsoang ke motsoako oa lithethefatsi o khothalletsang methylphenidate maemong a taolo ea 20 le lino tse tahang tsa 20, tseo boholo ba tsona li tsubang.

Lithutong tsohle, methylphenidate e eketsehile haholo dopamine ho striatum. Ho li-ventral striatum (moo li-nucleus accumbens li leng teng) le ho putamen, keketseho ea dopamine e ne e amahanngoa le litlamorao tse khotsofatsang tsa methylphenidate (ho rata lithethefatsi le ho phahama) mme li ne li kenelletse haholo ho lithethefatsi tsa joala (70 le 50% e tlase ho feta taolo, ka ho latellana). Ho li-taolo, empa eseng ho lino tse tahang, metabolism ho orbitofrontal cortex (sebaka se amehang ka sesepa factor) e ne e sa tsamaellane hantle le keketseho ea dopamine ea methylphenidate-induced dopamine. Liphetho tsena li tsamaisana le tšibollo ea maikutlo a hore orbitofrontal cortex e hlophisa boleng ba meputso ka ho laola boholo ba keketseho ea dopamine ka har'a ventral striatum le hore ho sitisoa ha molao ona ho ka fokolisa kutloelo-bohloko ea meputso lithutong tse lemaletseng.

inahaneloang

Boleng ba moputso (meputso ea tlhaho le lithethefatsi) bo amahanngoa le ho eketseha ha dopamine ka har'a li-nucleus tse bokellaneng mme li fapana joalo ka mosebetsi oa maemo. Cortex ea pele-pele e kentsoe molemong oa ho itšetleha ka moputso le ho boleng bo phahameng bo ntlafalitsoeng boo lithethefatsi li nang le tšebeliso ea lithethefatsi, leha mekhoa e sa utloisisoe hantle. Mona re leka hypothesis ea hore cortex ea pele e laola boleng ba meputso ka ho fetolela keketseho ea dopamine ka li-bokellase tsa nucleus le hore molao ona o sitisoa ho lithuto tse lemalloang. Re sebelisitse positron emission tomography ho lekola mosebetsi oa preortal cortex (ho lekanya metabolism ea glucose ea kelello le [18F] fluorodeoxyglucose) le keketseho ea dopamine (e lekantsoe le [11C] moralo, D2/D3 receptor ligand e nang le binding e amehang ho endo native dopamine) e khothalletsoang ke motsoako oa lithethefatsi o khothalletsang methylphenidate maemong a taolo ea 20 le lino tse tahang tsa 20, tseo boholo ba tsona li tsubang. Lithutong tsohle, methylphenidate e eketsehile haholo dopamine ho striatum. Ho li-ventral striatum (moo li-nucleus accumbens li leng teng) le ho putamen, keketseho ea dopamine e ne e amahanngoa le litlamorao tse khotsofatsang tsa methylphenidate (ho rata lithethefatsi le ho phahama) mme li ne li kenelletse haholo ho lithethefatsi tsa joala (70 le 50% e tlase ho feta taolo, ka ho latellana). Ho li-taolo, empa eseng ho lino tse tahang, metabolism ho orbitofrontal cortex (sebaka se amehang ka sesepa factor) e ne e sa tsamaellane hantle le keketseho ea dopamine ea methylphenidate-induced dopamine. Liphetho tsena li tsamaisana le tšibollo ea maikutlo a hore orbitofrontal cortex e hlophisa boleng ba meputso ka ho laola boholo ba keketseho ea dopamine ka har'a ventral striatum le hore ho sitisoa ha molao ona ho ka fokolisa kutloelo-bohloko ea meputso lithutong tse lemaletseng.

Selelekela

Keketseho ea dopamine (DA) e hokahane le likarabo tse matlafatsang tsa lintho tse sebelisoang tlhekefetso ho kenyeletsa joala (Koob et al., 1998), empa ts'ebetso ea litekanyetso tse lemalloang e sa hlakileng. Ho lumeloa hore tšebeliso ea lithethefatsi tse sa foleng e baka phetoho e feto-fetohang libakeng (lipotolohong) tse fetotsoeng ke DA tse tlatselletsang ts'ebetsong ea bongaka ba tahi (Robbins le Everitt, 2002; Nestler, 2004). Har'a tsena, "cortex" e tlang pele ho nako e ntse e amoheloa ka ho fetelletseng, e bapala karolo ea mantlha ea ho lemalla.Jentsch le Taylor, 1999). Haholo-holo a bohlokoa ke litletlebo tsa pele tsa tikoloho (VTA) le li-nucleus accumbens (NAc), tse phethang karolo ea bohlokoa taolong ea polao ea lisele tsa DA le tokollo ea DA, ka ho latellana (Gariano le Groves, 1988; Murase et al., 1993). Ka sebele, lithuto tsa pele ho tsa bophelo li tlalehile liphetoho tseleng ena e nang le tšebeliso e mpe ea lithethefatsi, tse ileng tsa khothaletsoa ho fokolisa taolo ea tšebeliso ea lithethefatsi tse bonts'ang bokhoba (White et al., 1995; Kalivas, 2004).

Morero oa thuto ena e ne e le ho lekola taolo ea tšebetso ea DA bokong ka cortex ea pele ho bokhoba ba tahi. Ho lekola tšebetso ea DA ea boko, re sebelisitse positron emission tomography (PET) le [11C] raclopride (DA D2/D3 receptor radioligand e nang le tieo e amehang tlholisanong le setho sa mehleng ea DA) ((Volkow et al., 1994a) pele le kamora phephetso ka intravenous methylphenidate (MP) mme o ile a bapisa likarabo lipakeng tsa 20 detoxified lino tse tahang le taolo e phetseng hantle ea 20. Re sebelisitse MP e le phephetso ea meriana hobane e eketsa DA ka ho thibela batsamaisi ba DA (li-DAT) mme ka hona e lumella tlhahlobo e sa tobang ea ts'ebetso ea sele ea DA (Volkow et al., 2002). Ho lekola tšebetso ea cortex ea pele, re lekantsoe metabolism ea "glucose metabolism" ea tikoloho, e sebetsang joalo ka letšoao la tšebetso ea boko (Sokoloff et al., 1977), o sebelisa PET le [18F] fluorodeoxyglucose (FDG). Mehopolo ea rona e neng e sebetsa e ne e le hore lithutong tse tahang, taolo ea tšebetso ea boko ea DA ka kotloloho e tlang pele e ka senyeha le hore ba ka be ba fokolitse tšebetso ea DA. Hape hobane ho eketseha ha li-DA tse hlohlellelitsoeng ke MP ke tsona li amanang le litlamorao tsa eona tse ntle (Volkow et al., 1999), re boetse re nahana hore ho fokotsoa ha tumello ea DA ho lino tse tahang ho ka lebisa ho soabisang hoa pono e nepahetseng ea litlamorao tse khahlisang tsa MP.

Lisebelisoa le mekhoa

Lintho.

Ho ithutile lithuto tse mashome a mabeli tsa joala le taolo ea banna ba 20. Makhoba a joala a ile a thaothoa ho tsoa lichabeng tsa bongaka le lipapatsong. Lethathamo 1 e fana ka palo ea batho le lithuto tsa bongaka. Bonyane lingaka tse peli li ile tsa buisana le bakuli ho etsa bonnete ba hore baa kopana Buka ea ho hlahloba le ea Statistical ea Mathata a kelello (DSM), ntlafatso ea bone, litekanyetso tsa ho hlahloba bokhoba ba tahi, ka tlhahlobo ea semmuso e hlophisitsoeng e sebelisang litekanyetso tsa DSM. Mekhoa ea ho kenyelletsa e boetse e hloka hore ba be le mong ka bona oa boemo ba pele eo e neng e le lekhoba la joala. Bafo ba ne ba qheleloa ka thoko haeba ba ne ba na le nalane ea ts'ebeliso e mpe ea lithethefatsi kapa bokhoba ba tahi (ntle le joala le nicotine). Mekhoa ea ho qheleloa ka thoko e boetse e kenyelletsa nalane ea mafu a kelello (ntle le ho itšetleha ka joala) kapa lefu la methapo, maemo a bongaka a ka fetolang ts'ebetso ea bokong (ke hore, lefu la pelo, la endocrinological, la oncological kapa la autoimmune), ts'ebeliso ea hajoale ea meriana e laetsoeng kapa e rekisoang. , le / kapa ts'itiso ea hlooho ka lebaka la tahlehelo ea kelello ea> 30 min. Lihlooho tsohle li ne li tšoenyehile Hamilton (Hamilton, 1959) le khatello ea maikutlo ea Hamilton (Hamilton, 1960) lintlha <19 mme o ile a tlameha ho ithiba ho noa joala bonyane 30 d pele ho thuto. Ho ile ha hiroa taolo ho tsoa lipapatsong tse likoranteng tsa lehae; Mekhoa ea ho khetholla ntle le kabelo ea ts'ebeliso ea joala kapa tšebeliso e mpe ea lithethefatsi e ne e ts'oana le ea lithuto tsa joala. Ntle le moo, lithuto tsa taolo li ne li sa kenyeletsoe haeba ba ne ba na le nalane ea lelapa ea joala. Lihlooho tsohle li ne li hlahlojoa 'meleng, kelellong le kelello. Lisebelisoa tsa lithethefatsi li entsoe matsatsing a lithuto tsa PET ho kenyelletsa tšebeliso ea lithethefatsi tse sebelisang kelello. Bafo ba ile ba laeloa hore ba khaotse ho sebelisa litlhare tse rekisoang libeke tse 2 pele ho scan ea PET, mme litsamaiso li laetsoe hore li tlohele ho noa joala beke pele ho scan ea PET. Lijo le lino (ntle le metsi) li ile tsa emisoa bonyane 4 h pele mme lisakerete li emisitsoe bonyane 2 h pele ho thuto. Phuputso ena e amohetsoe ke Boto ea Setsi ea Tlhahlobo ho Setsi sa Naha sa Brookhaven, mme tumello e ngotsoeng e nang le tsebo e fumanoe lihloohong tsohle.

Tafole 1. 

Lipontšo tsa palo ea batho ba laoloang ke lingaka le taolo ea tahi

Mehato ea boitšoaro le ea pelo.

Litekanyetso tse kenang (1-10) bakeng sa litlamorao tsa lithethefatsi li tlalehiloe pele le 27 min kamora ho tsamaisoa ha placebo kapa MP (Wang et al., 1997). Litlaleho tsena tsa boits'oaro ba litlamorao tsa lithethefatsi li bonts'oa li tšepahala ebile li ts'oana ho lithuto tsohle (Fischman le Foltin, 1991). Sekhahla sa pelo le khatello ea mali li ile tsa hlahlojoa pele le nako le kamora ho tsamaisoa ha placebo kapa MP.

Sekena.

Lithuto tsa PET li entsoe ka Nokia (Iselin, NJ) HR + tomograph (qeto, 4.5 × 4.5 × 4.5 mm e nang le bophara ba halofo-e phahameng) ka mekhahlelo e meraro. Lithuto tsohle li phethe lintlha tse peli tse entseng ka [11C] raclopride, le 19 ea li-taolo le 19 ea lino tse tahang e phethile scan ea boraro e entsoeng ka FDG. Sekolo se ile sa phetheloa ka nako ea 2 d, mme taelo ea etsoa ka tatellano. Mekhoa e phatlalalitsoe bakeng sa [11C] moralo oa leqhubu (Volkow et al., 1993a) le bakeng sa FDGWang et al., 1993). Bakeng sa [11C] raclopride scans, e 'ngoe ea likotlo tse peli e entsoe kamora ho kenella ka hare ho placebo (3 cc ea saline), e' ngoe e entsoe ka mor'a hore MPraraousous MP (0.5 mg / kg), ba fuoeng 1 min pele [11C] ente ea raclopride. Phuputso eo e ne e le moralo oa "cros temple" e sa boneng. Mekoallo ea matla a ile a qalisoa hang ka mor'a ho enteloa 4-10 mCi ea [11C] raclopride (tšebetso e ikhethileng, 0.5-1.5 Ci / μm qetellong ea bombardment) mme e fumanoe kakaretso ea 54 min. Mali a arter a ile a fumanoa hohle ho ts'ebetsong ho lekanya khatello ea ho se fetohe [11C] moralo ka bongata ka plasma joalo ka ha ho hlalositsoe pele (Volkow et al., 1993a). Bakeng sa FDG, mehato e ne e etsoa maemong a mantlha (ha ho na tšusumetso), 'me ho ile ha qalisoa tekanyetso ea metsotso e 20 ka mor'a ente ea 35-4 mCi ea FDG,' me mali a arterial a sebelisetsoa ho lekanya FDG ka lero la mali. Nakong ea ts'ebetso, bafo ba ile ba lula ba le maemong a holimo mahlo a bona a butsoe ka kamoreng e lefifi, 'me lerata le ne le fokotsoa hanyane. Methati ea metabolic e ne e sebetsoa ho sebelisoa katoloso ea mofuta oa Sokoloff (Phelps et al., 1979).

Tlhahlobo ea litšoantšo.

Bakeng sa [11Litšoantšo tsa C] morusu, libaka tse khahlisang (ROI) li fumanoe ka kotlolloho ho tsoa ho [11C] litšoantšo tsa raclopride joalo ka ha ho hlalositsoe pele (Volkow et al., 1994a). Ka bokhutšoanyane re khethile ROI ho litšoantšo tse akaretsitsoeng (litšoantšo tse matla tse nkiloeng ho 10 ho ea ho 54 min) tse ileng tsa sebelisoa hape ka sefofane se kopaneng moo re khethileng libaka ho caudate (CDT), putamen (PUT), ventral striatum (VS), le cerebellum . Likarolo tsena li ne li ka etsoa ka sekhahla bakeng sa ho fumana lintlha tsa C-11 le nako, e neng e sebelisoa ho bala K1 (tsamaisoa khafetsa ho tloha ho plasma ho ea ho lisele) le bophahamo ba phallo (DV), e lumellanang le tekanyo e lekanang ea karo-karolelano ea tishu ea mahlaseli ho mahlaseli a plasma ho CDT, PUT, le VS e sebelisa mokhoa oa ho hlahloba litšoantšo bakeng sa lits'ebetso tse fetohelang (Logan et al., 1990). Karo-karolelano ea DV ho striatum ho eo e leng cerebellum, e lumellanang B, max′ /Kd′ + 1 (Kd′ Le B, maxKe li sebetsang Ka vivo li-constantion moo boteng ba neurotransmitter le nonspecific), li sebelisitsoe joalo ka khakanyo ea D2/D3 phumaneho ea receptor (Logan et al., 1990). Litlamorao tsa MP ho [11C] raclopride e tlamang e ile ea hlakoloa joalo ka phetoho ea liperesente B, max′ /Kd′ Ho tsoa sebakeng

Bakeng sa litšoantšo tsa metabolic, re ile ra ntša ROI re sebelisa mokhoa oa ho itlhahisa ka mokhoa o ikhethileng joalo ka ha ho hlalositsoe pejana mme re buoa sampole (1) libaka tse khethiloeng esale pele [orbitofrontal cortex (OFC), cingulate gyrus (CG), dorsolateral prefrontal], hobane lithuto tsa preclinical li bonts'itse seo ba laola tokollo ea DA; (2) libaka tsa litereke (CDT, PUT, VS), hobane tsena ke liphofu tsa mantlha tsa liteishene tsa DA; (3) limbic limb (amygdala, hippocampus, insula), hobane le tsona ke litefiso tsa liteishene tsa DA; le (4) tsa libaka tsa thalmic, tsa nakoana, tsa parietal, tsa occipital le tsa cerebellar, tseo re li nkileng e le libaka tsa taolo (Volkow et al., 2006). Ka bokhutšoanyane, re ile ra qala ho etsa 'mapa oa litšoantšo tsa metabolic ho MNI (Montreal Neurological Institute) sebaka se tloaelehileng sa boko ho felisa phapang lipakeng tsa boko ba batho ka bomong. Ho etsa lipalo tsa ROI, re hlahisitse 'mapa o koahelang li-voxels tsohle tse tsamaellanang bakeng sa sebaka se fanoeng kamora likhokahanyo tsa software ea Talairach Daemon (Collins et al., 1995; Lancaster et al., 2000) ho setšoantšo sa FDG PET.

Tlhahlobo ea lipalo.

Litlamorao tsa MP ho K1 le ho D2/D3 phumaneho ea receptor (B, max′ /Kd′) Le liphapang tse lipakeng tsa lihlopha tsa mantlha le karabelo ea MP li ile tsa hlahlojoa le ANOVA e nang le ntlha e le 'ngoe (taolo le bokhoba ba tahi) le ntlha e le' ngoe ea sehlooho (placebo vs MP). Romella hoc t Ho ile ha sebelisoa liteko ho bona hore na maemo ana a fapana hakae. Ho lekola kamano lipakeng tsa liphetoho tse bakoang ke MP B, max′ /Kd'(Phapang e itšetlehileng) ka CDT, PUT, le VS le metabolism ea boko ba tikoloho, re sebelisitse tlhahlobo ea ntlafatso ea sehlahisoa sa Pearson mehatong ea metabolism. Ho leka li-hypotheses tse tharo tsa sehlooho tsa boithuto (1) tse taolo empa eseng litekong tsa joala literekeng tsa pele [CG, OFC, le dorsolateral prefrontal cortex (DLPFC)] li ka amahanngoa le liphetoho tse hlahisitsoeng ke MP B, max′ /Kd′ (Ho fapana hoa maemo), (2) eo MP e ileng ea etsa liphetoho ho eona B, max′ /Kd′ E ne e tla ba menyenyane ho matahoa ho feta taolo, le (3) e fetohang B, max′ /Kd′ Ho VS e ne e tla amahanngoa le litlamorao tse khahlisang tsa MP mme ka hona litekanyetso tsa "ho rata lithethefatsi" le "tse phahameng" li ne li tla ba tlase ho lino tse tahang ho feta taolo, re beha boemo ba bohlokoa ho p <0.05. Bakeng sa tlhahlobo ea tlhahlobo ho lekola likamano lipakeng tsa liphetoho ho B, max′ /Kd"(E itšetlehileng ka ho fapana) le metabolism ho li-11 ROIs tse neng li sa hlalosoe pele, re beha bohlokoa ho p <0.005. Ho tiisa hore likamano li bonts'a ts'ebetso ea lebatooa ho fapana le ts'ebetso e phethahetseng ea ts'ebeliso ea metaboli, re boetse re lekotse likamano lipakeng tsa metabolic ea tikoloho e tloaelehileng (metabolism ea tikoloho / metabolism e felletseng ea boko). Liphapang lipakeng tsa likamano lipakeng tsa lihlopha li ile tsa lekoa ho sebelisoa liteko tse akaretsang tsa liketsahalo tse etsahetseng nakong e fetileng.

Hobane lithutong tse fetileng re bone khokahano lipakeng tsa litekanyetso tsa motheo tsa D2/D3 ho fumaneha ha li-receptor le metabolism ea pele ho ba hlekefetsang cocaine le methamphetamine (Volkow et al., 1993b, 2001), hape re ile ra lekola li-amanang tsena ho bona hore na mokhatlo o tšoanang o hlahile lithutong tsa joala (bohlokoa bo behiloe ho p <0.05).

Results

Likarolo tsa Plasma tsa MP

Lits'oants'o tsa Plasma (ka li-nanograms ka millimeter) li ne li sa fapana pakeng tsa lithuto le taolo ea joala ho 10 min (116 ± 26 vs 107 ± 16, ka ho latellana), 30 min (85 ± 25 vs 76 ± 12,, 45 (65 ( vs 15 ± 59). Ts'oarello ea plasma MP ha e kopane le liphetoho tse bakiloeng ke MP B, max′ /Kd′.

Likarabo tsa boitšoaro mabapi le MP

Ka lihlopha tsena ka bobeli, MP haholo (p <0.005) e eketsehile ka bongata litlalehong tsa hau tsa ho ikutloa e le sethethefatsi, ho phahama, ho hloka botsitso, ho susumetsoa, ​​lithethefatsi, ho rata lithethefatsi, ho se rate lithethefatsi, takatso ea joala le takatso ea koae (Lethathamo 2). Phello ea tšebelisano e ne e le bohlokoa bakeng sa litlaleho tse ngata tsa boithati tsa litlamorao tsa lithethefatsi (ntle le ho hloka botsitso le takatso ea joala) (Lethathamo 2). Romella hoc t Liteko li senotse hore litlamorao tsa MP li ne li le kholo haholo ho li-control ho feta lino tse tahang tse phahameng (p <0.003), e hlohlellelitsoe (p <0.003), utloa sethethefatsi (p <0.004), sethethefatsi se setle (p <0.04), le ho rata lithethefatsi (p <0.04) hape ba ne ba le lekhoba la joala ho feta takatso ea koae (p <0.002) le ho se rate lithethefatsi (p <0.05).

Tafole 2. 

Litlamorao tsa boitšoaro ba MP tse kenang ka har'a taolo le lithutong tsa joala le F boleng ba 'nete ea lithuto tse phetoang ANOVA bakeng sa sehlopha, lithethefatsi, le litlamorao

MP e ile ea eketsa lebelo la pelo le khatello ea mali ea systolic le diastolic, mme litlamorao tsena li ne li sa fapana lipakeng tsa lihlopha (data e sa bonts'itsoeng).

Mehato ea DA D2/D3 phepelo ea receptor ho baseline (placebo)

Motheo oa motheo, ho ne ho se na phapang lipakeng K1 lipakeng tsa lihlopha tsa cerebellum, CDT, PUT, kapa VS (Lethathamo 3). Ho fapana le hoo, D2/D3 phumaneho ea receptor (B, max′ /Kd′) E bonts'itse phello e kholo ea sehlopha ho VS (p <0.007) empa ha ho na liphapang ho CDT le PUT. Romella hoc t tlhahlobo e bonts'a VS D2/D3 ho fumaneha ha li-receptor ho ne ho le tlase haholo ho lino tse tahang (p <0.05) (Lethathamo 3).

Tafole 3. 

Mehato ea K1 'me B, max′ /KdBakeng sa [11C] litšoantšo tsa raclopride bakeng sa taolo le lithuto tsa joala bakeng sa placebo (PL) le maemo a MP, hammoho le p boleng ba liphetho tsa ANOVA bakeng sa sehlopha, lithethefatsi, le litlamorao tsa tšebelisano

Mehato ea DA D2/D3 ho fumaneha ha receptor kamora hore MP (DA e fetohe)

ANOVA ho K1 Mehato e senotse hore lithethefatsi kapa litlamorao ha li bohlokoa ho CDT, PUT, VS, kapa cerebellum, e bonts'a hore MP ha e fetole phepelo ea radiotracer le hore ha ho na phapang lipakeng tsa lihlopha (Lethathamo 3).

MP e fokotsehile B, max′ /Kd′, Mme ANOVA e hlahisitse phello e kholo ea lithethefatsi ho CDT (F = 19; p <0.001), PUT (F = 54; p <0.0001), le VS (F = 41; p <0.001), e bontšang seo B, max′ /Kd′ E fokotsoe haholo ke MP ka lihlopha tsena ka bobeli (bona Feie. 2, Lethathamo 3). Phello ea tšebelisano e ne e le bohlokoa bakeng sa PUT (F = 5.5; p <0.03) le VS (F = 13; p <0.001), e bonts'ang likarabo libakeng tsena li fapane lipakeng tsa lihlopha. The post hoc t Teko e senotse hore liphokotso tse nang le MP li ne li le nyane haholo ho lithethefatsi tsa joala ho PUT (taolo, 21% vs lino tse tahang, 11%; p <0.03) le VS (taolo, 27% vs lino tse tahang, 8%; p <0.002) (Feie. 1, Lethathamo 3).

Setšoantšo sa 1. 

Karolelano ea litšoantšo tsa DVR (DVR) bakeng sa [11C] lebala la marang-rang bakeng sa taolo (n = 20) le bokhoba ba tahi (n = 20) boemong ba striatum kamora placebo le kamora MP. Hlokomela ho fokotseha hoa tlamahano e ikhethileng (litekanyetso tsa DV) le MP le karabelo e fihletsoeng ea MP ho lithuto tsa joala ha li bapisoa le taolo.

Ho lekola hore na liphetoho tse nyane li B, max′ /Kd′ (PUT le VS) ho batho ba lemaletseng joala ho feta ho laoleng ba bonts'a bongata ba bona ba tsubang, re bapisa batho ba tsubang ho tloha sehlopheng ka seng mme ba bonts'a tse latelang: (1) batsamaisi ba tsubang (n = 3) e bile le liphetoho tse ts'oanang ho feta tse neng li se (n = 17) ho PUT (20 vs 21%, ka ho latellana) le VS (35 vs 26%, ka ho latellana); le (2) lekhoba la joala le tsubang (n = 16) e bile le liphetoho tse ts'oanang ho feta tse neng li se (n = 4) ho PUT (11 vs 12%, ka ho latellana) le VS (8 vs 6%, ka ho latellana).

Le ha lisampole li le nyane haholo hore li ka hlahisa sephetho se hlakileng, ha ho lipapiso tsena ho tsona tse ileng tsa fetoha B, max′ /Kd′ Tse nyane ho batho ba tsubang, tse fanang ka maikutlo a hore liphetoho tse nyane tsa lino tse tahang ha li bakoe feela ke ho tsuba.

Metabolism ea "glucose" ea "metabolism" ea tlhaho le ho ikamahanya le liphetoho tse hlahisitsoeng ke MP B, max′ /Kd′ Le mehato ea mantlha ea D2 ho fumaneha ha mokamo

Ha ho na bokong ka botlalo (taolo, 36.4 ± 4 μmol / 100 g / min; lino tse tahang, 35.0 ± 4 μmol / 100 g / min) kapa metabolism ea potoloho e sa fapana lipakeng tsa lihlopha (data e sa bontsitsoeng).

Ka taolo, liphetoho tse hlahisitsoeng ke MP B, max′ /Kd'VS li ne li hokahane hampe le metabolism sebakeng sa OFC [sebakeng sa Brodmann (BA) 11: r = 0.62, p <0.006; BA 47: r = 0.60, p <0.008], DLPFC (BA 9: r = 0.59, p <0.01), CG (BA 32: r = 0.50 p <0.04; BA 24: r = 0.52, p <0.03), le insula (r = 0.63; p <0.005). (Feie. 2). B, max′ /KdLiphetoho tsa CDT le PUT li ne li amana feela le metabolism ho CG (r > 0.51; p <0.03). Ho makhoba a tahi, likamano lipakeng tsa liphetoho tse bakiloeng ke MP ho B, max′ /Kd′ Le metabolism ea tikoloho e ne e se bohlokoa (Feie. 2). Papiso ea matsoalo a phallang lipakeng tsa lihlopha e senotse hore li-amanang li fapana haholo ka OFC (z = 2.3; p <0.05), DLPFC (z = 2.2; p <0.05), CG (z = 2.2; p <0.05), le insula (z = 2.6; p <0.01).

Setšoantšo sa 2. 

Boemo ba ho theoha ha lipakeng tsa liphetho li fetoha B, max′ /Kd′ (Tse fapaneng tse fapaneng) ho VS le tšebetso ea 'mele ea metabolic e felletseng ho OFC (BA 11), anterior CG (BA 32), le DLPFC (BA 9) maemong a laolang (mekoloko e tlatsitsoeng) le ho lino tse tahang. Hlokomela hore liperesente li fokotseha ho tlamello e tobileng ea [11C] moralo oa leqhubu (B, max′ /Kd′) E bonts'a ho nyoloha ha DA, 'me ka hona, regression e fana ka khokahano e mpe: ha metabolism e le tlase, le ho feta ha DA e eketseha.

Lihokelo le mehato e tloahelehileng ea metabolic (mkoa / metabolism eohle ea kelello) li ne li bohlokoa feela bakeng sa liphetoho lipakeng B, max′ /Kd′ Ho VS le OFC (r = 0.62; p <0.006) taolong empa eseng ho makhoba a tahi (Feie. 3). Kamano ena e fapana haholo lipakeng tsa lihlopha (z = 2.1; p <0.05).

Litumellano le motheo B, max′ /Kd′ (D2 ho fumaneha ha li-receptor) le metabolism ea tikoloho e ne e le bohlokoa bakeng sa lino tse tahang empa li sa laoloe ho CG (CDT: r = 0.57, p <0.02; ETSA: r = 0.59, p <0.01; VS: r = 0.57, p <0.02) le DLPFC (CDT: r = 0.52, p <0.03; ETSA: r = 0.52, p <0.03; VS: r = 0.50, p <0.03).

Kopano lipakeng tsa liphetoho tse fetisitsoeng ke MP B, max′ /Kd′ Le litlamorao tsa eona tsa boitsoaro le nalane ea ho noa le ho tsuba

Liphetoho ho B, max′ /Kd′ Ho VS e kopantsoeng le phahameng (r = 0.40; p <0.01), sethethefatsi se setle (r = 0.33; p <0.05), thabile (r = 0.33; p <0.05), ho hloka botsitso (r = 0.38; p <0.02), 'me ea hlohlelletsoa (r = 0.45; p <0.005); PUT ka phahameng (r = 0.32; p <0.05), sethethefatsi se setle (r = 0.34; p <0.05), 'me ea hlohlelletsoa (r = 0.46; p <0.005); le ho CDT ka ts'usumetso (r = 0.32; p <0.05).

Setšoantšo sa 3. 

Boemo ba ho theoha ha lipakeng tsa liphetho li fetoha B, max′ /Kd′ (Phetoho e itšetlehileng ka eona) ho VS le tšebetso e tloaelehileng ea metabolic ho OFC (boko bohle) maemong a taolo (mekoloko e tlatsitsoeng) le ho lino tse tahang (mekoloko e bulehileng).

Ha ho nalane ea joala kapa ea ho tsuba e amanang le liphetoho tsa B, max′ /Kd′ Ha lino tse tahang kaofela li kenyelelitsoe. Leha ho le joalo, ha ho ne ho hlahlobisisoa feela lino tse tahang tse tsubang, ho bile le khokahano lipakeng tsa liphetoho ho B, max′ /Kd′ Le lilemo tsa ho tsuba (PUT: r = 0.73, p <0.002) le lilemo tsa ho qala ho tsuba (PUT: r = 0.63, p <0.009; VS: r = 0.53, p <0.05).

Puisano

Taolo ea mantlha ea liphetoho tse entsoeng ke DA ea MP-e susumetsang lithutong empa e se lino tse tahang

Ka taolo, re bonts'a kamano e mpe pakeng tsa ts'ebetso ea metabolic e phethahetseng libakeng tse tlang pele (OFC, CG, DLPFC) le liphetoho tse hlahisitsoeng ke MP B, max′ /Kd′ (Hakanyetso ea liphetoho tsa DA) ho VS le PUT. Ntle le moo, khokahano ena e lutse ho OFC kamora ho tloaela tšebetso ea 'mele oa metabolic e bonts'a hore, bonyane ho OFC, e hlophisitsoe ka kotloloho tikolohong. Phumano ena e lumellana le lithuto tsa precinical tsa ho ngola melao ea pele ho lisele tsa DA ho VTA le tokollo ea DA ho NAc (Gariano le Groves, 1988; Murase et al., 1993).

Ho fapana le lino tse tahang, metabolism libakeng tse tlang pele e ne e sa amanngoe le liphetoho tsa DA (joalo ka ha ho hlahlojoa le liphetoho ho B, max′ /Kd′). Sena se fana ka maikutlo a hore bokhobeng ba tahi, molao oa tšebetso ea lisele tsa DA ka mesebetsi ea pele e sitisoa le hore tšebetso ea bona ea lisele e fokotsehileng ea DA e ka bonts'a tahlehelo ea taolo ea tseleng ea DA mesolimbic. E 'ngoe ea likheo tsa mantlha tsa lisele tsa DA ho VTA ke lintho tse bonojoang ke moea o tsoang ka bokhabane tse tsoang cortex ea pele.Carr le Sesack, 2000), mme ho na le bopaki bo ntseng bo hola ba hore ba bapala karolo ea bohlokoa ho bokhoba ba tahi (Kalivas le Volkow, 2005). Liphuputso tse entsoeng esale pele li boetse li bonts'itse hore tšusumetso ea karolo ea pele ea cortex mabapi le melao ea boitšoaro e fokotseha ka tsamaiso e sa feleng ea lithethefatsi e kenyang tahlehelo ea taolo taolong ea bokhoba ba tahi (Homayoun le Moghaddam, 2006). Ntle le moo, ho sitisoa ha OFC (tikoloho e kenyelletsoeng ka sesosa sa tšohanyetso, ho sitisoa ha eona ho amanang le boits'oaro bo potlakileng) le CG (sebaka se amehang le taolo ea thibelo, tšitiso ea sona e amanang le ho qobelloa) e nkuoa e le karolo ea mantlha ts'ebetsong ea bokhoba ba tahi (Volkow et al., 2003).

Tlhahlobo e hlalositsoeng e senoletse hore maemong a taolo, liphetoho tsa DA ho VS le tsona li ne li kopantsoe le metabolism ho insula. Insula ke e 'ngoe ea libaka tse nang le tikoloho e kholo e nang le ts'oaetso ea DA.Gaspar et al., 1989), mme patlisiso e sa tsoa etsoa e tlalehang hore tšenyo ea ho ts'ireletso e nepahetseng e ne e hokahanngoa le ho khaotsa ho tsuba ho pepesetsang bohlokoa ba eona ba ho lemalla (Naqvi et al., 2007).

Ho theoha ho lokolloa ha DA lithutong tsa joala

Bokhobeng ba joala, MP e entse keketseho e nyane haholo ea DA ho VS le PUT ho feta litulong. MP ke blocker ea DAT, mme bakeng sa boemo bo itseng ba li-blockade tsa DAT, liphetoho tsa DA li bonts'a palo ea DA e ikemetseng e lokollotsoeng (Volkow et al., 1999). Hobane khatello ea MP ho plasma, e neng e sa fapana lipakeng tsa lihlopha, e bolela esale pele maemo a thibelo ea DAT (Volkow et al., 1998, 1999), karabelo e sa utloahaleng ea MP e fana ka maikutlo a hore lino tse tahang li lokollotsoe ho feta lipehelo tsa DA. Lits'ireletso li anngoe haholo ho VS (70% e tlase ho feta taolo), e lumellanang le liphetho tsa pejana tsa keketseho ea DA ho VS kamora amphetamine ho lino tse tahang (50% e tlase ho feta taolo) (Martinez et al., 2005). Liphumano tsena li lumellana le lithuto tsa pele tse bontšang ho fokotseha ho hoholo ha ho hlaseloa ha cell cell (Diana et al., 1993; Bailey et al., 1998; Shen et al., 2007) ho VTA mme ea fokotseha DA ho NAc (Weiss et al., 1996) Kamora ho khaotsa joala bo sa foleng. Ho boela o theoloa hoa tsela ea DA VTA-ea ho bokella joala ho ka ba beha kotsing ea ho sebelisa joala bo bongata ho lefella khaello ena. Ha e le hantle, taolo e matla ea tahi e khutlisetsa tšebetso ea lisele tsa VTA DA liphoofolong tse tšoaroang hampe ke joala (Diana et al., 1996; Weiss et al., 1996).

Lithethefatsi li boetse li bonts'itse keketseho ea li-DA tse kentsoeng ke MP-e kenyelletsang ka PUT (47% e tlase ho feta taolong). Sena se ka etsahala se bonts'a ho kenella ha lisele tsa DA ho substantia nigra, e ts'epahallang PUT mme e amehile ka boits'oaro ba makoloi. Khaello ea DA ho PUT e ka hlalosa ho ba kotsing e kholo ea matšoao a makoloi a tsoang ho lingaka tse tahang.Shen, 1984).

Boithuto ba pejana ho ba hlekefetsang koae bo boetse bo ngotsitse phokotso ea bohlokoa ho keketseho ea DA e entsoeng ke MP (50% e tlase ho feta taolo) (Volkow et al., 1997), e bonts'ang hore mesebetsi e fokotsehileng ea lisele tsa DA e kanna ea bonts'a tlhekefetso e le 'ngoe ea ho lemalla.

Fokotsa likarabo tse matlafatsang ho MP e kenang ka har'a joala

Likarabo tse khahlisang tse monate tsa MP ho joala joala li ne li le tlase ho feta taolong. Taba ea hore litla-morao tsena tsa MP li amana le keketseho ea DA ho VS e bonts'a hore likarabo tse matlafatsoang tsa MP li bonts'itse mosebetsi o fokotsehileng oa sele ea VTA. Ho isa tekanyong ea hore lisele tsa VTA DA, ka karolo ea tsona e nahannoeng ho NAc, li kenya letsoho ho fetoleng likarabo tse matlafatsang ho batšireletso ba lithethefatsi tse fokotsehileng li fokotsehile ts'ebetso ea lisele tsa DA e ka fokotsang kutloisiso e fokolisitsoeng ea meputso e se nang joala ho lino tse tahang (Hlakola et al., 2007).

Joala / Mokokotlo oa nicotine

Lithutong tsa joala tse neng li tsuba, liphetoho tse bakoang ke DA li ile tsa lumellana le nalane ea tsona ea ho tsuba. Mokhatlo ona o ka bonts'a likarabo tse tloaelehileng ho joala le ho tsuba hobane nicotine e sa foleng le eona e fokotseha hoa ts'ebetso ea boits'oaro ea lisele tsa VTA DA (Liu le Jin, 2004). Leha ho le joalo, hobane liphetoho tsa DA li ne li sa fapana pakeng tsa batho ba tsubang joala le batho ba sa tsubeng kapa ba sa tsubeng, ho ke ke ha etsahala hore litheko tsa DA li hlahisoe feela ke ho tsuba empa li ka bonts'a likotsi tse tloaelehileng ('Nete et al., 1999; Bierut et al., 2004; Le et al., 2006).

Motheo DA D2/D3 mehato ea li-receptor

Motheo DA D2/D3 fumaneha ka "receptor" e ne e le tlase ho lino tse tahang ho feta taolong ea VS, e lumellanang le monahano o fetileng (Heinz et al., 2004; Shen et al., 2007) le postmortem (Tupala et al., 2001, 2003) lithuto.

Motheo D2/D3 ho fumaneha ha li-receptor ka har'a lino tse tahang (empa eseng ka har'a taolo) ho ne ho amana le metabolism ho CG le DLPFC. Sena se lumellana le liphumano tse fetileng tsa cocaine le bahanyetsi ba methamphetamine le lithutong tse kotsing e kholo ea liphatsa tsa lefutso tseo ho tsona re tlalehileng kamano le lipakeng tsa mantlha striatal D2/D3 ho fumaneha ha li-receptor le metabolism ea pele (Volkow et al., 1993b, 2001, 2006). Leha ho le joalo, e fapana le likamano lipakeng tsa liphetoho tsa pele tsa metabolism le liphetoho tse bakoang ke DA, tse neng li le bohlokoa bakeng sa taolo empa eseng bakeng sa lino tse tahang. Sena se kanna sa bonts'a taba ea hore li tsamaisana le mehato e fapaneng ea li-neurotransmission tsa DA; liphetoho ho B, max′ /Kd′ Bonts'a tokollo ea DA ho li-neuron tsa DA, e leng ts'ebetso ea ho thunya lisele tsa DA ebile e hlophisoa ke tšebetso ea pele, athe D2/D3 ho fumaneha ha li-receptor hangata ho bonts'a maemo a receptor ao mohlomong a fetotsoang ke liphatsa tsa lefutso le epigenetic empa, tsebong ea rona, eseng ka ts'ebetso ea pele. Kahoo, kamano e lipakeng tsa motheo oa D2/D3 li-receptors ho ka etsahala hore li bonts'e phetoho ea dopaminergic ea libaka tsa pele tsa cortical (Maobane le Halliday, 1987). Ho joalo, ho lino tse tahang, ho fokotsa ho fumaneha ha D2R ho VS ho bontšitsoe ho amahanngoa le takatso e matla ea tahi le ts'ebetso e kholo ea cueex ea cialex ea cialex le anterior ea CG ha ho hlahlojoa le monahano o sebetsang oa matla a matla a khoheli (Heinz et al., 2004).

Motheo oa metabolism ea "glucose" ea tikoloho

Phuputsong ena, ha rea ​​ka ra bonts'a phapang ho metabolism ea "glucose metabolism" (ho kenyelletsa le cortex ea frontal) lipakeng tsa taolo le lino tse tahang. Sena se fapana le lithuto tse fetileng, tse bonts'itseng phokotso ho metabolism ea joala (litlhahlobo) Wang et al., 1998). Leha ho le joalo, hobane phokotso ea metabolism ea boko e fola haholo ka hara libeke tsa 2-4 tsa detoxation (haholo-holo ho cortex ea kapele)Volkow et al., 1994b), ho sitoa ho bona ho fokotseha lithutong tsa rona ho ka supa taba ea hore ba ne ba tlohetse joala bonyane 30 d pele ho thuto.

sheba mefokolo ea

Pele, hobane [18F] FDG, e na le halofo ea bophelo ba 120 min, ho ne ho se bonolo ho e etsa [11C] mehato ea li-raclopride ka letsatsi le le leng (10 h e hlokahala pakeng tsa liente). Leha ho le joalo, hobane methapo ea methapo ea methapo ea methapo ea methapo le mehato ea liphetoho tse bakoang ke liphetoho tsa MP li tsitsitse ha lithuto li hlahlojoa ka matsatsi a arohaneng (Wang et al., 1999a,b), likhokahano li kanna tsa ba li tšoana haeba ho bile le monyetla oa ho li leka ka letsatsi le le leng.

Taba ea bobeli, li-amanang le CG, DLPFC, le insula li ne li se bohlokoa ha ts'ebetso e ne e tloaelehile ho metabolism ea boko bohle, kahoo libakeng tsena, mekhatlo e lokela ho nkuoa e le ea pele. Hape, khokahano ha e bolele hore mekhatlo ea batho ba qobelloang kapa hona ho fana ka tataiso, ka hona re ke ke ra hlakisa hore mokhatlo ha e na ho bonts'a taolo ea pele ea tokollo ea DA e bonts'a phetoho ea DA ea libaka tsa pele.

Taba ea boraro, motheo oa D2/D3 phumaneho ea receptor ha e lekantsoe le [11C] raclopride e ka bonts'a maemo a tlase a receptor kapa ho nyolla ha DA (Gjedde et al. 2005). Leha ho le joalo, taba ea hore lino tse tahang, ha li fuoa MP, e bonts'itse tokollo ea DA e bonts'a mehato e tlase ea D2/D3 ho fumaneha ha li-receptor ka har'a lino tse tahang ho bontša, joalo ka ha ho tlalehiloe ke lithuto tsa postmortem (Tupala et al., 2003), maemo a tlase a D2 li-receptors.

Qetellong ho tsuba ho ferekanya, empa hobane ∼90% ea makhoba a joala (Batel et al., 1995), lintho tseo re li fumaneng li amana le tlhekefetso ho bongata ba lino tse tahang.

fihlela qeto e

Liphetho tsena li tsamaisana le khopolo ea tahlehelo ea tšitiso ea mantlha ea tšebetso ea lisele tsa DA ho lino tse tahang le ho fokotseha ho hoholo hoa tšebetso ea DA lithutong tsena. Kamano lipakeng tsa keketseho ea DA e atileng ho VS le likarabo tse fokotsoang tsa moputso ho MP li fana ka maikutlo a hore litlolo tsa DA li ka baka tlatsetso e bakoang ke bokhoba ba tahi mme li ka kenya letsoho kotsing ea tsona ea ts'ebeliso e mpe ea joala e le mokhoa oa ho lefella bofokoli bona. Liphumano tsena li fana ka maikutlo a hore ho nka bohato ba ho khutlisetsa melaoana pele le bosholu ba DA li ka ba molemo ho bakuli ba joala.

Mongolo o botlaaseng ba leqephe

  • E amohetse Julayi 25, 2007.
  • Nchafatso e amohetse Mphalane 2, 2007.
  • E amohetse Mphalane 2, 2007.

  • Mosebetsi ona o ile oa tšehetsoa ke karolo ea Intramural Research Program ea National Institutes of Health-National Institute on Alcoholism and Alcohol Abuse, ke Lefapha la Matla (Ofisi ea Biology le Tikoloho ea Tikoloho, konteraka DE-AC01-76CH00016), le National Institute of Mental Health Grant MH66961-02. Re leboha Donald Warner ka ts'ebetso ea PET; David Schlyer le Michael Schueller bakeng sa ts'ebetso ea cyclotron; David Alexoff le Paul Vaska bakeng sa taolo ea boleng ba mehato ea PET; Colleen Shea, Lisa Muench, le Youwen Xu bakeng sa motsoako oa radiotracer; Pauline Carter bakeng sa tlhokomelo ea booki; Karen Apelskog bakeng sa khokahano ea protocol; le Linda Thomas bakeng sa thuso ea bongoli.

  • Litaba li lokela ho lebisoa ho Dr. Nora D. Volkow, Setsi sa Naha sa Tlhekefetso ea Lithethefatsi, 6001 Executive Boulevard, Kamore ea 5274, Bethesda, MD 20892. [imeile e sirelelitsoe]

References

  1. ↵
    1. Bailey CP,
    2. Manley SJ,
    3. Watson WP,
    4. Wonnacott S,
    5. Molleman A,
    6. Little HJ

    (1998) Tsamaiso e sa foleng ea taolo ea ethanol e sa fetoheng mesebetsing ea methapo ea kutlo e sa sebetseng ka mor'a ho emisa hyperexcitability. Resin ea Boko 24: 144-152.

  2. ↵
    1. Batel P,
    2. Pessione F,
    3. Maitre C,
    4. Rueff B

    (1995) Kamano lipakeng tsa joala le ho ts'oara koae ho batho ba tsubang joala. lemalla ntho e 90: 977-980.

  3. ↵
    1. Bierut LJ,
    2. Rice JP,
    3. Goate A,
    4. Hinrichs AL,
    5. Saccone NL,
    6. Lisa K
    7. Edmond HJ,
    8. Cloninger CR,
    9. Be Heloise H,
    10. Kakaretso PM,
    11. Crowe RR,
    12. Hesselbrock V,
    13. Li TK,
    14. Nurnberger JI Jr.,
    15. Porjesz B,
    16. Schuckit MA,
    17. Reich T

    (2004) Tlhahlobo ea genomic ea ho tsuba tloaelo malapeng a batho ba lemaletseng tahi: mabaka a tloaelehileng le a ikhethang a ts'ebeliso ea lithethefatsi. Ke J Med Genet A 124: 19-27.

  4. ↵
    1. Carr DB,
    2. Sesack SR

    (2000) Morero o tsoang ho "preortalal cortex" ea tikoloho ho ea sebakeng sa sephetho sa sephetho: sepheo se tobileng mekhatlong ea li-synaptic e nang le liaccaccants le li-mesocortical neurons. J Neurosci 20: 3864-3873.

  5. ↵
    1. Collins DL,
    2. Holmes CJ,
    3. Peters TM,
    4. Evans AC

    (1995) Karolo e ikemetseng ea 3-D e ikemiselitseng Hum Brain Mapp 3: 190-208.

  6. ↵
    1. Diana M,
    2. Pistis M,
    3. Carboni S,
    4. Graham GL,
    5. Rossetti ZL

    (1993) Ho fokotseha ho hoholo hoa ts'ebetso ea mesolimbic dopaminergic neuronal nakong ea ethanol ea ho khaola ha tlhaho ho bopaki ba rats electrophysiological le biochemical. Proc Natl Acad Sci USA 90: 7966-7969.

  7. ↵
    1. Diana M,
    2. Pistis M,
    3. Muntoni A,
    4. Gessa G

    (1996) Mesolimbic dopaminergic kupunguza e bontša mofuta oa ho emisoa oa ethanol: bopaki ba ho khaotsa ho se sebetse. Khopolo-taba 71: 411-415.

  8. ↵
    1. Fischman MW,
    2. Foltin RW

    (1991) Ts'ebeliso ea litekanyo tsa litlamorao tse tlisoang ke ho hlahloba mokoloto oa lithethefatsi ho batho. Br J Addict 86: 1563-1570.

  9. ↵
    1. Gariano RF,
    2. E fana ka PM

    (1988) Ho thunya ho hoholo ho bakiloeng ke li-neuron tsa dbamine tsa midbrain ka ho hlohlelletsa li-cortices tsa methapo ea methapo le ea pele. Resin ea Boko 462: 194-198.

  10. ↵
    1. Khopoli P,
    2. Berger B,
    3. Febru A,
    4. Vigny A,
    5. Henry JP

    (1989) Catecholamine innervation ea cortex ea motho ea mokokotlo joalokaha e senotsoe ke immunohistochemistry ea tyrosine hydroxylase le dopamine-beta-hydroxylase. J Comp Neurol 279: 249-271.

  11. ↵
    1. Gjedde A,
    2. Wong DF,
    3. Rosa-Neto P,
    4. Cumming P

    (2005) Ho etsa li-neuroreceptors tsa 'mapa ho mosebetsi: ka tlhaiso-leseling ea lintho tse tlamang ka mora ts'ebetso ea lilemo tsa 20. Int Rev Neurobiol 63: 1-20.

  12. ↵
    1. Hamilton M

    (1959) Tlhahlobo ea matšoenyeho e re ka tekanyetso. Br J Med Psychol 32: 50-55.

  13. ↵
    1. Hamilton M

    (1960) Tekanyo ea tekanyo ea khatello ea maikutlo. J Neurol Neurosurg Psychiatry 23: 56-62.

  14. ↵
    1. Heinz A,
    2. Siessmeier T,
    3. Ngola J,
    4. Hermann D,
    5. Klein S,
    6. Grusser SM,
    7. Flor H,
    8. Braus DF,
    9. Buchholz HG,
    10. Ground G,
    11. et al a.

    (2004) Kamano pakeng tsa li-receptor tsa dopamine D (2) ho li-ventral striatum le ho sebetsa bohareng ba litheko tsa joala le litakatso. Am J Psychiatry 161: 1783-1789.

  15. ↵
    1. Homayoun H,
    2. Moghaddam B

    (2006) Tsoelo-pele ea liphetoho tsa cellular ho cortex ea medial pele le orbitofrontal ha e arabela amphetamine e phetoang. J Neurosci 26: 8025-8039.

  16. ↵
    1. Jentsch JD,
    2. Taylor JR

    (1999) Ho potlaka ho bakoang ke ho se sebetse hantle ha tšebeliso e mpe ea lithethefatsi: litlamorao bakeng sa taolo ea boitšoaro ka tšusumetso e amanang le moputso. Psychopharmacology (Berl) 146: 373-390.

  17. ↵
    1. Kalivas PW

    (2004) Mekhoa ea Glutamate e lemaletseng koae. Curr Opin Pharmacol 4: 23-29.

  18. ↵
    1. Kalivas PW,
    2. Volkow ND

    (2005) Motheo oa neural oa bokhoba: mokhoa oa tšusumetso le khetho. Am J Psychiatry 162: 1403-1413.

  19. ↵
    1. Koob GF,
    2. Roberts AJ,
    3. Schulteis G,
    4. Parsons LH,
    5. Heyser CJ,
    6. Hyytia P,
    7. Merlo-Pich E,
    8. Weiss F

    (1998) Lipheo tsa Neurocircuitry ho moputso oa ethanol le ho its'epahalla. Mofuta Oa Kliniki 22: 3-9.

  20. ↵
  • ↵
    1. LE AD,
    2. Li Z,
    3. Funk D,
    4. Shram M,
    5. Li TK,
    6. Shaham Y

    (2006) Ho ba kotsing ea ho itaola le ho ts'oara ts'oaetso ea litloholo tse se nang lino tse tahang bakeng sa joala haholo. J Neurosci 26: 1872-1879.

  • ↵
    1. Liu ZH,
    2. Jin WQ

    (2004) Ho fokotseha hoa ts'ebetso ea methapo ea methapo ea methapo ho dopamine neuronal ho litoeba tsa ho ntša nikotine. NeuroReport 15: 1479-1481.

  • ↵
    1. Logan J,
    2. Fowler JS,
    3. Volkow ND,
    4. Wolf AP,
    5. Dewey SL,
    6. Scmyer khaled,
    7. MacGregor RR,
    8. Hitzemann R,
    9. Bendriem B,
    10. Gatley SJ,
    11. Christman DR

    (1990) Tlhahlobo ea bocha ea radioligand e tlamang ho latela mehato ea ts'ebetso ea nako e sebelisitsoeng ho lithuto tsa [N-11C-methyl] - (-) - Cocaine PET lithuto tsa batho. J Cereb flow flow Metab 10: 740-747.

  • ↵
    1. Martinez D,
    2. Gil R,
    3. Slifstein M,
    4. Hwang DR,
    5. Huang Y,
    6. Perez A,
    7. Kegeles L,
    8. Talbot P,
    9. Evans S,
    10. Krystal J,
    11. Laruelle M,
    12. Abi-Dargham A

    (2005) Ho itšetleha ka joala ho kopantsoe le phetisetso ea dopamine e sa tlatsuoang kahare ho "ventral striatum". Biol Psychiatry 58: 779-786.

  • ↵
    1. Murase S,
    2. Grenhoff J,
    3. Khoa G,
    4. Gonon FG,
    5. Svensson TH

    (1993) Pele cortex e laola ho phatloha ho hoholo le ho tsamaisoa ha transmitter ho rat mesolimbic dopamine neurons tse ithutoang ho vivo. Neurosci Lett 157: 53-56.

  • ↵
    1. Naqvi NH,
    2. Rudrauf D,
    3. Damasio H,
    4. Bechara A

    (2007) Tšenyo ea ts'usumetso e kenya ts'usumetso ea ho lemalla ho tsuba. Science 315: 531-534.

  • ↵
    1. Nestler EJ

    (2004) Mekhoa ea limolek'hule tsa bokhoba ba lithethefatsi. Neuropharmacology 47 (Suppl 1): 24-32.

  • ↵
    1. Orent RD,
    2. Halliday GM

    (1987) Sisteme ea Ventral tegmental (A10): neurobiology. 1. Anatomy le kgokelo. Resin ea Boko 434: 117-165.

  • ↵
    1. Phelps ME,
    2. Huang SC,
    3. Hoffman EJ,
    4. Selin C,
    5. Sokoloff L,
    6. Kuhl DE

    (1979) Tekanyo ea Tomographic ea tekanyo ea "metabolism" ea "" c "glucose metabolism ho batho ba nang le (F-18) 2-fluoro-2-deoxy-D-glucose: netefatso ea mokhoa. Ann Neurol 6: 371-388.

  • ↵
    1. Robbins TW,
    2. Everitt BJ

    (2002) Lits'ebetso tsa ho ikhopotsa limbic-striatal le bokhoba ba lithethefatsi. Neurobiol Ithute Mem 78: 625-636.

  • ↵
    1. Shen RY,
    2. Choong KC,
    3. Thompson AC

    (2007) Phokotso ea nako e telele sebakeng sa ts'ebetso ea sebaka sa dopamine tsa dopamine neuron ka mor'a ts'usumetso e pheta-phetoang kapa ethanol. Biol Psychiatry 61: 93-100.

  • ↵
    1. Shen WW

    (1984) Matšoao a extrapyramidal a amanang le ho khaotsa joala. Biol Psychiatry 19: 1037-1043.

  • ↵
    1. Sokoloff L,
    2. Reivich M,
    3. Kenneth C,
    4. Des Rosiers MH,
    5. Patlak CS,
    6. Pettigrew KD,
    7. Sakurada O,
    8. Shinohara M

    (1977) Mokhoa oa [deoxyglucose oa [14C] bakeng sa litekanyo tsa ts'ebeliso ea tsoekere ea likhalase tsa lehae: mohopolo, ts'ebetso, le litekanyetso tse tloaelehileng mokokotlong oa albino e hlokometsoeng. J Neurochem 28: 897-916.

  • ↵
    1. True WR,
    2. Xian H,
    3. Scherrer JF,
    4. Madden PA,
    5. Bucholz KK,
    6. Heath AC,
    7. Eisen SA,
    8. Lisna MJ,
    9. Khahla J,
    10. Tsuang M

    (1999) Ho ba kotsing ea tlhaho ea lefutso le ts'oaetso ea nicotine le joala ho banna. Arch Gen Psychiatry 56: 655-661.

  • ↵
    1. Tupala E,
    2. Hall H,
    3. Bergstrom K,
    4. Sarkioja T,
    5. Rasanen P,
    6. Mantere T,
    7. Hoa C,
    8. Hiltunen J,
    9. Tiihonen J

    (2001) Dopamine D (2) / D (3) -receptor le li-density tsa transporter ho li-nucleus accumbens le amygdala tsa mofuta oa 1 le lino tse tahang tsa 2. Mol Psychiatry 6: 261-267.

  • ↵
    1. Tupala E,
    2. Hall H,
    3. Bergstrom K,
    4. Mantere T,
    5. Rasanen P,
    6. Sarkioja T,
    7. Tiihonen J

    (2003) Dopamine D2 receptors le baeti ka mofuta oa 1 le lino tse tahang tsa 2 tse lekantsoeng le human hemisphere autoradiography. Hum Brain Mapp 20: 91-102.

  • ↵
    1. Volkow ND,
    2. Fowler JS,
    3. Wang GJ,
    4. Dewey SL,
    5. Scilyer D,
    6. MacGregor R,
    7. Logan J,
    8. Alexoff D,
    9. Shea C,
    10. Hitzemann R,
    11. Angrist B,
    12. Wolf AP

    (1993a) Ho hlahisa mehato e pheta-phetoang ea carbon-11-raclopride e tlamang bokong ba motho. J Nucl Med 34: 609-613.

  • ↵
    1. Volkow ND,
    2. Fowler JS,
    3. Wang GJ,
    4. Hitzemann R,
    5. Logan J,
    6. Scmyer khaled,
    7. Dewey SL,
    8. Wolf AP

    (1993b) Ho fumaneha ha dopamine D2, ho kopantsoe le amanang le metabolism e fokotsitsoeng ea botlhole ba koae. Synapse 14: 169-177.

  • ↵
    1. Volkow ND,
    2. Wang GJ,
    3. Fowler JS,
    4. Logan J,
    5. Scilyer D,
    6. Hitzemann R,
    7. Lieberman J,
    8. Angrist B,
    9. Pappas N,
    10. MacGregor R,
    11. Burr G,
    12. Cooper T,
    13. Wolf AP

    (1994a) Tlholisano ea dopamine ea morao-rao ea maqhubu a dopamine e nang le [11C] raclopride bokong ba motho. Synapse 16: 255-262.

  • ↵
    1. Volkow ND,
    2. Wang GJ,
    3. Hitzemann R,
    4. Fowler JS,
    5. Ka kakaretso JE,
    6. Burr G,
    7. Wolf AP

    (1994b) Pholoso ea "metabolism" ea "glucose metabolism" ho batho ba lemaletseng joala. Am J Psychiatry 151: 178-183.

  • ↵
    1. Volkow ND,
    2. Wang GJ,
    3. Fowler JS,
    4. Logan J,
    5. Gatley SJ,
    6. Hitzemann R,
    7. Chen AD,
    8. Dewey SL,
    9. Pappas N

    (1997) E ile ea fokotsa karabelo ea dopaminergic e ntlafalitsoeng lithutong tse itšetlehileng ka koae. Nature 386: 830-833.

  • ↵
    1. Volkow ND,
    2. Wang GJ,
    3. Fowler JS,
    4. Gatley SJ,
    5. Logan J,
    6. Ding YS,
    7. Hitzemann R,
    8. Pappas N

    (1998) Dopamine transporter e kenang bokong ba motho e susumetsoa ke litekanyetso tsa kalafo tsa methylphenidate ea molomo. Am J Psychiatry 155: 1325-1331.

  • ↵
    1. Volkow ND,
    2. Wang GJ,
    3. Fowler JS,
    4. Gatley SJ,
    5. Logan J,
    6. Ding YS,
    7. Dewey SL,
    8. Hitzemann R,
    9. Gifford AN,
    10. Pappas NR

    (1999) blockade ea ba tsamaisang dopamine ba tsamaisang dopamine ka methylphenidate e kenang ha e ea lekana ho itlisetsa litlaleho tsa "phahameng." J Pharmacol Exp Ther 288: 14-20.

  • ↵
    1. Volkow ND,
    2. Chang L,
    3. Wang GJ,
    4. Fowler JS,
    5. Ding YS,
    6. Sedler M,
    7. Logan J,
    8. Franceschi D,
    9. Gatley J,
    10. Hitzemann R,
    11. Gifford A,
    12. Wong C,
    13. Pappas N

    (2001) Boemo bo tlase ba li-receptor tsa dopamine ea D2 ho bahlaseli ba methamphetamine: setsoalle le metabolism ho cortex ea orbitofrontal. Am J Psychiatry 158: 2015-2021.

  • ↵
    1. Volkow ND,
    2. Wang GJ,
    3. Fowler JS,
    4. Logan J,
    5. Franceschi D,
    6. Maynard L,
    7. Ding YS,
    8. Gatley SJ,
    9. Gifford A,
    10. Zhu W,
    11. Swanson JM

    (2002) Kamano lipakeng tsa blockade ea ba tsamaisang dopamine ka methylphenidate ea molomo le keketseho ea dopamine ea extracellular: litlamorao tsa kalafo. Synapse 43: 181-187.

  • ↵
    1. Volkow ND,
    2. Fowler JS,
    3. Wang GJ

    (2003) Boko ba motho ea lemaletseng: lintlha tse tsoang thutong ea monahano. J Clin 111: 1444-1451.

  • ↵
    1. Volkow ND,
    2. Wang GJ,
    3. Be Heloise H,
    4. Porjesz B,
    5. Fowler JS,
    6. Telang F,
    7. Wong C,
    8. Ma Y,
    9. Logan J,
    10. Goldstein R,
    11. Alexoff D,
    12. Thanos PK

    (2006) Tekanyo e phahameng ea li-receptor tsa dopamine D2 ho litho tse sa angoeng ke malapa a joala: lintlha tse ka khonehang tsa tšireletso. Arch Gen Psychiatry 63: 999-1008.

  • ↵
    1. Wang GJ,
    2. Volkow ND,
    3. Roque CT,
    4. Cestaro VL,
    5. Hitzemann RJ,
    6. Cantos EL,
    7. Levy AV,
    8. Dhawan AP

    (1993) Bohlokoa ba ts'ebetso ea ho atoloha ha ventricular le atrophy ea cortical lithutong tse phetseng hantle le lino tse tahang joalo ka liteko tsa PET, MR imaging, le liteko tsa neuropsychologic. Radioloji 186: 59-65.

  • ↵
    1. Wang GJ,
    2. Volkow ND,
    3. Hitzemann RJ,
    4. Wong C,
    5. Angrist B,
    6. Burr G,
    7. Pascani K,
    8. Pappas N,
    9. Lu A,
    10. Cooper T,
    11. Lieberman JA

    (1997) Litlamorao tsa ho ba le boitšoaro le pelo le methapo ea methapo ea methapo lithutong tse tloaelehileng le ba hlekefetsang koae. Khokahano ea Res 3: 49-54.

  • ↵
    1. Wang GJ,
    2. Volkow ND,
    3. Fowler JS,
    4. Pappas NR,
    5. Wong Kahs,
    6. Pascani K,
    7. Felder CA,
    8. Hitzemann RJ

    (1998) metabolism ea "cerebral metabolism" ho joala bo tahang ba basali ha e tšoane le ea taolo. Mofuta Oa Kliniki 22: 1850-1854.

  • ↵
    1. Wang GJ,
    2. Volkow ND,
    3. Levy AV,
    4. Felder CA,
    5. Fowler JS,
    6. Pappas NR,
    7. Hitzemann RJ,
    8. Wong CT

    (1999a) E lekanya tlhahiso ea likarabo tsa metabolism tsa boko tsa tikoloho ho lorazepam sebelisa limmapa tsa lipalo. J Nucl Med 40: 715-720.

  • ↵
    1. Wang GJ,
    2. Volkow ND,
    3. Fowler JS,
    4. Logan J,
    5. Pappas NR,
    6. Wong Kahs,
    7. Hitzemann RJ,
    8. Netusil N

    (1999b) Ho hlahisa lipampiri tsa khafetsa tsa tlholisano ea dopamine ea endo native le [11C] raclopride bokong ba motho ha a arabela methylphenidate. J Nucl Med 40: 1285-1291.

  • ↵
    1. Weiss F,
    2. Parsons LH,
    3. Schulteis G,
    4. Hyytiä P,
    5. Lorang MT,
    6. Bloom FE,
    7. Koob GF

    (1996) Ts'ebetso ea boithati ea Ethanol e khutlisetsa bofokoli bo amanang le ho tlosoa ho dopamine e futsanehileng le tokollo ea 5-hydroxytryptamine ka litoeba tse itšetlehileng. J Neurosci 16: 3474-3485.

  • ↵
    1. White FJ,
    2. Hu XT,
    3. Zhang XF,
    4. Wolf ME

    (1995) Ts'ebetso e pheta-phetoang ea likarabo tsa "cocaine" kapa "amphetamine alters" ho hlahisa glutamate tsamaisong ea dopamine ea tsebaccumbens. J Pharmacol Exp Ther 273: 445-454.

  • ↵
    1. Ngola J,
    2. Schlagenhauf F,
    3. Kienast T,
    4. Kopano T,
    5. Bermpohl F,
    6. Kahnt T,
    7. Beck A,
    8. Strohle A,
    9. MOKHATLO OA BOHLOKOA:
    10. Knutson B,
    11. Heinz A

    (2007) Ho se sebetse hantle hoa amanang le ho lokisa moputso hammoho le litakatso tsa joala ho batho ba lemaletseng joala. NeuroImage 35: 787-794.

    • Lihlooho tse qotsitsoeng sehloohong sena