Li-Agonists tsa Dopamine li Fokotsa Bohlokoa ba ho Sensitivity ea Orbitofrontal Cortex: Tlhahlobo ea Papali ea Litlhapi Bophelong ba Parkinson? (2009)

Neuropsychopharmacology. Sengoloa se ngotsoeng; e fumaneha ho PMC 2010 Dec 1.

E hatisitsoe ka mokhoa o qetelle o hlophisitsoeng e le:

PMCID: PMC2972251

KAMISELO: CAMS1534

Thilo van Eimeren, 1,2,3 Bénédicte Ballanger, 1,3 Giovanna Pellecchia, 1,3 Janis M Miyasaki,2Anthony E Lang, 2 le Antonio P Strafella1,2,3, *

Phetolelo ea ho qetela ea sengoliloeng sa sengoliloeng sena e fumaneha mahala ho Neuropsychopharmacology
Sheba lihlooho tse ling ho PMC hore Qotsa sehlooho se hatisitsoeng.
 

inahaneloang

Lintho tse buuoang ka ho hlaka tsa papali ea papali ea marang-rang ha li utloisisehe hantle. Tlhahisoleseling e ka fumanoa ka ho utloisisa litlamorao tsa pharmacological tsamaisong ea moputso ho bakuli ba nang le lefu la Parkinson (PD). Phekolo ea li-dopamine agonists (DAs) e 'nile ea amahanngoa le ho becha ha methapo ho bakuli ba PD. Leha ho le joalo, hore na li-DA li kentse letsoho joang ntlafatsong ea mofuta ona oa bokhoba ha bo tsejoe. Re lekile maikutlo a hore tšusumetso ea tonic receptors ea dopamine ka ho khetheha e nyenyefatsa tsamaiso ea moputso oa dopaminergic ka ho thibela ho fokotseha ha phetiso ea dopaminergic e etsahalang ka karabelo e mpe. Re sebelisa monahano o sebetsang oa matla a phello ea matla, re ithutile bakuli ba PD nakong ea likarolo tse tharo tsa moputso oa phenabilistic ka tatellano: ho tsoa kalafo, kamora kalafo ea levodopa (LD), le kamora tekanyetso e lekanang ea DA (pramipexole). Bakeng sa teko e 'ngoe le e' ngoe, boleng ba phello ea polelo ea moputso e ne e ngotsoe ho sebelisoa sephetho, thupa le menyetla. Pramipexole e fetotse ts'ebetso ea orbitofrontal cortex (OFC) ka kotloloho ka mekhoa e 'meli eo ka bobeli e amanang le kotsi e kholo ea ho kenya ts'ebetsong matla a makenete. Liphetoho tse hlahisitsoeng ke sepheo li ne li phahame haholo ka pramipexole ha e bapisoa le LD kapa meriana. Ntle le moo, ke pramipexole feela e fokotsitseng khokahano ea liteko ka teko ka litekanyetso tsa phoso ea ho bolela esale pele. Tlhahlobo e 'ngoe e hlahisitse hore sena se hlahisitsoe haholo ke ho se sebetse hantle ha liteko litekong tse nang le liphoso tse mpe tse boletsoeng esale pele mabapi le moputso. Re fana ka tlhahiso ea hore li-DA li thibele ho khumama ha phetisetso ea dopamine ebe ka tsela e joalo e fokotsa matla a ho matlafatsa a fokolisang. Seo re se fumaneng se hlahisa potso ea hore na ho becha ho ka ba teng ka tšohanyetso ho tsoa phihlelong e mpe ea OFC ho tataisa boits'oaro ha e tobane le litlamorao tse mpe.

Keywords: fMRI, khatello ea taolo ea tšusumetso, dopamine agonist, moputso, ho lemalla, ho matlafatsa

SELELEKELA

Papali ea chelete ea papali ea chelete - e le mokhoa o seng kotsi bakeng sa batho ba bangata, e ka fetoha mokhoa o lematsang le o kotsi ho papali ea papali ea chelete. E ts'oanang le ts'ebeliso ea lithethefatsi, PG e na le likarolo tsa mamello, ho tlohela, kapa ho etsa lintho tse ling () mme hangata e bitsoa 'temallo ea boitšoaro' (). Leha PG, e ts'oanang le bokhoba ba lithethefatsi, e hokahane le liphetoho phetohong ea moputso oa dopaminergic, tlhahiso ea boleng, le ts'ebetso ea ho fana ka maikutlo (; ; ), liphoso tsa neurobehaeveal tsa PG li lula li sa utloisisehe. Tseleng ea kutloisiso ea PG, kananelo e hlakileng ea litlamorao tsamaisong ea meriana ho bakuli ba nang le lefu la Parkinson (PD) e kanna ea ba letšoao la bohlokoa. Ho lahleheloa ke phetiso ea dopaminergic ho PD e amahanngoa le boits'oaro bo bobe ba ho nka kotsi bo ka tlase.; ). Leha ho le joalo, ho qala ts'ebetso ea phekolo ea dopamine ho amana le nts'etsopele ea PG (; ). Le ha ho le joalo, ho fihlela joale, tlhaiso-leseling e sa lekanyetsoang ea nako e telele e fumaneha ho fana ka maikutlo a mofuta o itseng oa kalafo (bakeng sa tlhahlobo ), liphuputso tsa morao-rao li bonts'a hore kotsi ea ho nts'etsapele PG e eketseha ka ho khetheha ha e phekoloa le dopamine agonists (DAs) ha e bapisoa le kalafo ntle le DA (; ; ). Ka mokhoa o makatsang, phello ea lethalinyana ha e-so ka e fumanoa bathong bohle ba mokuli, athe ho mokuli a le mong ea nang le PG, monyetla oa lethalinyana o ka bonahala (;). Le ha ho sa hlokahale hore ho be le ts'usumetso ea kelello ho rona, re nahana hore, ho nts'etsapele PG, motsoako oa litlhare tse tloaelehileng o sebetsana le tšekamelo e kenang ho mokuli ka mong. Boithuto bona bo shebisisa sekhahla se ka 'nang sa e-ba teng ka sehlahisoa sa limela ka ho ithuta tlhekefetso e tsamaisoang ke DA ts'ebetsong ea moputso ho bakuli ba PD.

Mefuta ea khomphutha e sebetsanang le moputso, phoso e boletsoeng esale pele ea moputso (RPE) e emela phapano lipakeng tsa moputso o lebelletsoeng ebe o hlile o fumanoe (). Ho lokolloa ha dopamine ea mesolimbic neurons ho bontša boleng ba RPE hantle haholo. Liphoso tse nepahetseng ponelopele ea moputso (ke hore, 'ho feta-ho lebelletsoe') li hlahisoa ke ho phatloha ho hoholo hoa phasic of dopamine neuron firing (; ). Ka lehlakoreng le leng, liphoso tse mpe tse boletsoeng esale pele mabapi le moputso (ke hore, 'tse mpe ho feta tse lebelletsoeng') li lebisa ho khefu ea phasic ho thunya ha dopamine (; ). Joalo ka ha li bapisoa le levodopa (LD), 'me li khothalletsa li-dopamine receptors, re fana ka tlhahiso ea hore li-DA li ka thibela likotlo phetisetso ea dopamine mme ka tsela eo li sitisa matla a ho matlafatsa a lahlehang. Le ha phello ea neurobehaeveal ena e ka eketsa kotsi ea ho ba le PG, bopaki bo hlakileng ba kamano ena boa fokola.

Mona, re ithutile bakuli ba PD ntle le kalafo ea "dopamine", kamora LD, le kamora kalafo ea DA ha ba ntse ba etsa papali ea 'roulette' nakong ea ts'ebetso ea matla a kelello a resonance imaging (fMRI). Re sebelisa mesebetsi e ts'oanang, lithuto tsa FMRI tsa pejana li ile tsa atleha ho tsamaisa katleho molemong oa moputso oa dopaminergic ka ho sebelisa boleng ba RPE joalo ka regressor (; ). Re ne re thahasella (i) ho bolela phetoho ea tšebetso kamora ho latela maikutlo, le (ii) ho hokahana ha liteko ka litekanyetso tsa RPE — e le sesupo sa ts'ebetso ea meputso ea lehae. Ho qoba litlamorao tsa boitšoaro bo botle nakong ea fMRI, re ile ra lekola boits'oaro bo ka ipehang kotsing ka ntle ho naha.

Motheong oa khopolo-taba ea hore li-DAs li thibela phetisetso ea dopaminergic e nang le litekanyetso tse mpe tsa RPE, re boletse esale pele hore ho fapana le OFF le LD, DAs e tla eketsa ts'ebetso e hlahisang tlhahiso-leseling mme e nyenyefatse sistimi ea moputso ho RPE. Re boetse re khothaletsa hore boikemisetso ba moputso bo tla amahanngoa le boits'oaro bo eketsehileng ba ho beha bophelo kotsing mosebetsing.

LISEBELISOA LE MEKHOA

barupeluoa ba

Bakuli ba robeli ba letsohong le letona (lilemo, ho bolela ± SD: 56 ± 9 lilemo) le nako ea pele ea PD (nako ea lefu, ho bolela ± SD: 4 ± 3 lilemo li ngolisitsoe thupelong. Mekhoa ea bona ea meriana e khahlanong le Parkinsonia e ne e kenyelletsa motsoako oa LD (tekanyetso ea letsatsi le letsatsi, e bolelang ± SD: 594 ± 290 mg) le pramipexole (lethal dose la letsatsi le letsatsi, ho bolela ± SD: 2.3 ± 1.1 mg). Re khethile bakuli ntle le nalane ea maemo a holimolimo a neuropsychiatric (ho kenyeletsa khatello ea maikutlo, 'dementia' kapa bothata bofe kapa bofe ba taolo ea tšusumetso). Beck Depression Inventory II (bolela ± SD: 7 ± 5), Montreal Cognitive Assessment (bolela ± SD: 27 ± 2), le Barratt Impulsivity Scale-11 (bolela ± SD: 71 ± 10) li ne li sebelisoa ho lekola sekhukhu. khatello ea maikutlo, ho senyeha ha kelello, le ho ts'oaroa ha motho ka mong, ka ho latellana. Lithuto tsohle li fane ka tumello e ngotsoeng e ngotsoeng ea ho nka karolo. Boithuto bona bo amohetsoe ke Komiti ea Boitšoaro ea Lipatlisiso bakeng sa University Health Network, Toronto.

Bakuli ba ile ba ithutoa ka linako tse tharo mantsiboeeng a fapaneng (libeke tsa 1-3 ka thoko). Phekolo ea Dopamine e khutlisetsoa ntle le 12 h pele ho karolo e 'ngoe le e' ngoe. Ka tatellano e hanyetsanang, bakuli ba ile ba ithuteloa bongaka (OFF), kamora ho tsamaisoa ka molomo ba LD (100mg LD + 25mg benserazide), kapa lethal dose le lekanang la DA (1mg pramipexole) (Setšoantšo sa 1a). Bakuli ba bile le ts'ebetso e nkang kotsi ea 37 ± 7 min kamora ho tsamaisoa ha lithethefatsi, 21 ± 5 min hamorao, karolo ea motor ea Unified PD Rating Scale e ile ea hlahlojoa ke ngaka ea methapo e sebetsanang le mathata a ho sisinyeha le 13 ± 2 min hamorao, moputso oa lichelete oa probabilistic mosebetsi o entsoe nakong ea fMRI e amanang le liketsahalo.

Setšoantšo sa 1 

Moralo oa ho ithuta. (a) Kamora ho khaola bosiu ka bongaka meriana e khahlanong le Parkinsonia, bakuli ba nang le lefu la parkinson (PD) ba ile ba ithuteloa ka tatellano e sa reroang: ho sebelisa meriana (OFF), kalafo ea levodopa (LD), le kamora tekanyetso e lekanang ea pramipexole ...

Mosebetsi o Kotsi

Mosebetsi oa ho nka likotsi tsa Balloon Analogue ke kotsi ea maikutlo eo motho ka mong a ka e nkang kapa a lahleheloa ke chelete (). Barupeluoa ba pompa balune e hlahisitsoeng skrineng ka ho tobetsa konopo ea khomphutha. Bakeng sa pompo e 'ngoe le e' ngoe, fantisi e skrineng e eketseha ka lisente tsa 5. Kamora palo e sa lebelloang ea lipompo, balune e ka phatloha, ea baka tahlehelo ea chelete e bokelletsoeng ka kontinenteng. Barupeluoa ba ileng ba ntša lipompo tse eketsehileng (lipompo tse fetotsoeng) ba ne ba nkuoa ba ikemiselitse ho beha likotsi (). Re ile ra hlahloba litlamorao tsa meriana tlhahlobisong ea phapang (ANOVA) re sebelisa STATISTICA bakeng sa Windows 6.0 (www.statsoft.com).

Mosebetsi oa Moputso oa mohlomong

Mosebetsi ona oa k'homphieutha o tšoana le papali ea papali ea lipalesa (Setšoantšo sa 1b). Kamora ho potoloha ho potoloha le lebili la roulette la stationary, bolo e ile ea thella 'me ea emisa ho 1 ea lipokotho tse mebala tsa 16 (4 ea e' ngoe le e 'ngoe: e mosehla, e khubelu, e putsoa, ​​e putsoa). Morupeluoa o ile a tlameha ho hakanya 'mala oa pokotho eo bolo e tla emisa ka ho khetha e' ngoe ea likhetho tse 'ne: halofo ea liteko, o ile a tlameha ho khetha pakeng tsa mebala e mene e hapiloeng (monyetla oa ho hapa, 0.25); halofong e 'ngoe, o ne a tlameha ho khetha pakeng tsa makhetlo a mane a mebala e hapileng (monyetla oa ho hapa, 0.75). Kota e tekong e filoeng e kanna ea ba 1 kapa 5 Canada dollars. Lenaneo la khomphutha le hlahisitse tatellano ea pseudo-randomized ea mekhahlelo ena ea liteko (litekanyetso tse tharo tse fapaneng tse hlophisitsoeng li sebelisitsoe ka tatellano). Qeto ea mokhahlelo oa ketso eo e leng khetho ea motho ea nkang karolo e ne e le khetho eo a ka e khethang. Haeba bolo e ne e emisa ka pokothong e pentiloeng ho e 'ngoe ea mebala e hapileng, thupa e ne e hapiloe. Ho seng joalo, e ile ea lahleha. Ho ahlola ho fapana ka lebaka la monyetla, tatellano ea ho hapa le ho lahleha e ile ea hlophisoa hape ea kenyeletsoa sengolong sa nako eo (lenaneo le ile la etsa hore bolo e emise ka pokothong e itseng). Lekarete tsa pele e ne e le $ 20. Moralo oa pele oa nyeoe o hlahisitse thupa (ekaba chelete ea $ 1 kapa tefiso ea $ 5) le likhetho tsa 2 s (Setšoantšo sa 1b, holimo). Qeto e ne e lokela ho etsoa kahare ho 3 s e latelang (e bonts'itsoeng ke barbar ea ho bala). Haeba ho ne ho se na konopo e hatelletsoeng nakong eo, lenaneo le ne le ikhethile ka khetho e le 'ngoe. Lenaneo le ile la emisa haeba seo se etsahetse makhetlo a mararo ka tatellano. Sekhetlo sa bobeli sa teko se kentse lebili la roulette (Setšoantšo sa 1b, 2nd ho tloha holimo). Ha bolo e ntse e potoloha (8 s), thupa e ile ea bontšoa bohareng ba lebili; khetho e khethiloeng le tekanyo e bonts'itsoe ka tlase ho lebili, 'me 0.5 s ka mor'a hore bolo e emise, sephetho se bonts'itsoe (3 s) bohareng ba lebili (letšoao la algebraic le palo; enke e tala bakeng sa ho hapa; enke e khubelu bakeng sa ho lahleheloa) 'me chelete e fetotsoe ka ho lekana (Litšoantšo 1b, 3rd ho tloha holimo). Litefiso tsa ho qetela li ile tsa lefuoa ka chelete.

Bakuli ba ile ba bapala papali ena (Java 2 Platform Standard Edition 5.0; Sun Microsystems Inc, Santa Clara, CA) nakong ea fMRI e apere li-gogles tsa video le ho bontša liqeto ka ho tobetsa likonopo mabokoseng a karabo a behiloeng ka letsohong le leng le le leng (mabokose le likhahla, Resonance Technology, Los Angeles, CA, USA). Ka tatellano e lokiselitsoeng ea liteko tsa 280, chelete e setseng ha e e-so ka e ea ka tlase ho 0 mme chelete ea ho qetela e ne e le $ 8, $ 10, kapa $ 12 (li khahlanong le linako tse ling). Ho qoba mokhathala, re arola papali ka makhetlo a robong, e 'ngoe le e' ngoe e sa feleng ea 9. Tlhokomeliso e ile ea hlahlojoa ka ho rekota linako tsa karabelo le likarabelo tsa karabelo.

RPE Model

Boithutong ba fMRI ba ts'ebetso ea moputso, boleng ba RPE bo sebelisitsoe ho etsa mohlala oa data ea FMRI (; ), ho nka kamano lipakeng tsa boleng ba RPE le letšoao la mali le oksijene ea mali (BOLD) sebakeng sa ts'ebetso ea moputso. Re sebelisa mosebetsi o nang le menyetla e lekantsoeng le e hlakileng, re ka bontša boleng ba polelo ea moputso joalo ka sehlahisoa sa arithmetic sa thupa le menyetla ea ho hlola. Boleng ba RPE bo emela phapano lipakeng tsa boleng ba sephetho le boleng ba ponelo ea moputso (boleng ba sephetho − boleng ba ponelo ea moputso = boleng ba sephetho− (palo x ea monyetla oa ho hapa) (Setšoantšo sa 1c).

FMRI Skanning le Tlhahlobo ea Boitsebiso

U sebelisa sekepe sa 3 T GE MRI, lifoto tsa T2 * tse bobebe tse nang le BOLD bapisoa li fumanoe 2.23 s ka makhetlo a robong le lipalo tsa 245. Setšoantšo sa tšimo se ne se etselitsoe ho koahela bokaholimo ba bokopa, bohare le bohareng ba mpa. Meqolo e na le likhechana tsa 30 oblique (3 mm, ha ho na lekhalo), boholo ba li-voxel tsa lifofane e ne e le 2mm × 2 mm. Litšoantšo li ile tsa sebetsoa le ho hlahlojoa ho sebelisoa software ea SPM5 (http://www.fil.ion.ucl.ac.uk/spm). Likarolo tse peli tse qalang tsa matha ka seng li ile tsa lahloa ho lumella matla a tsitsitseng a mmuso. Litšoantšo tse setseng li ile tsa fetisetsoa setšoantšong sa pele 'me tsa hlophisetsoa ka nepo ho template e tloaelehileng (MNI 305). Litšoantšo tse tloaelehileng li ile tsa hlakisoa hantle ka kernel ea Gaussian ea 8mm ka halofo e bophara bo felletseng ho fokotsa phapang pakeng tsa thuto ea mantlha le ho nolofalletsa ts'ebeliso ea mohopolo oa tšimo ea Gaussian.

Litlhahlobo tsa boemo ba pele li ne li etsoa ka thoko bakeng sa thuto e 'ngoe le e' ngoe le boemo ba bongaka bo bong le bo bong ho latela mofuta oa kakaretso oa mola). Phetoho ea letšoao la lehae la BOLD e ile ea etsoa ho sebelisoa li-regressor tse arohaneng bakeng sa ho qala (ho khothaletsoa ka ts'ebetso ea karabo ea hemodynamic) ho e 'ngoe ea liketsahalo tse latelang: tlhahiso ea thupa le likhetho; tobetsa ea konopo; qalo ea bolo; sephetho. Joaloka kholomo e 'ngoe ka har'a matrix a moralo, ho boleloa hore litekanyetso tse lokisitsoeng tsa RPE li ile tsa hlahisoa e le regressor e arohaneng ho hlalosa phetoho ea lets'oa la BOLD nakong ea sephetho. Litšoantšo tse fapaneng li le 'ngoe (ka' ngoe, boemo ba meriana, le seboka) bakeng sa lipapatso tse hlakileng tse hlahisang phetoho e BONOLO (e ngoe ho regressor ea ketsahalo) le khokahano ea phetoho ena ka boleng ba RPE (ngoe ho RPE regressor) e kentse li-ANOVA tse arohantsoeng tse fapaneng le tse ling hape. lintlha tsa 'taba' (maemo a 8) le 'meriana' (maemo a 3; TSO, LD, DA) ho etsa papiso e bohlale ea voxel ea phetoho ea lets'oao la BOLD. Re nkile mothating oa lipalop<0.05 (kamora tokiso ea sekhahla sa ho sibolla ha bohata) e le bohlokoa ().

Ntle le moo, re fuputse tlhahlobo e ka bang teng litabeng tsa litlamorao tse hlahang tlhahlobisong e boletsoeng ka holimo. Haholo-holo re ne re batla ho bona hore na litlamorao tsa DA tsa bohlasoa li lumellana le boits'oaro bo kotsing ba ho beha kotsing ea ts'ebetso ea kotsi ea analogue ea Balloon. Ho fihlela sena, re hlahisitse sekhahla sa motho ka mong mosebetsing oa ho nka likotsi tse ka re ntšang kotsi (lipompo tse fetotsoeng) ka mokhoa oa ts'ebetso ho li-ANOVA (tlhahlobo e le 'ngoe ea tlhahlobo, tšebelisano' moho le 'meriana').

LIPOTSO

Likolo le Lipalo

Joalokaha ho lebelletsoe, palo ea makoloi ea Unified PD rating Scale e ntlafalitsoe ka bobeli ka LD (19.6 ± 7.9) le DA (21.5 ± 9.2) ha e bapisoa le OFF (27.5 ± 9.9) tLiteko: DA vs. TSOHLE p<0.01; LD vs. TSOHLE p<0.01; DA vs. LD p= 0.16). Ho sebelisa litlhare ha hoa ka ha ama mekhoa ea ho ba hlokolosi mosebetsing oa fMRI. Linako tsa karabelo (bolela ± SD: OFF 1270 ± 300 ms; LD 1329 ± 419 ms; DA 1250 ± 349 ms) and omissions majibu (bolela ± SD: OFF 9.75 ± 5.2 ms; LD 9.25 ± 5.6 ms; DA 9.75 ± 3.1 ms ) ha ea fapana pakeng tsa maemo (linako tsa karabelo: F (2, 21) = 0.12, p= 0.90; likarabelo tsa karabelo: F (2, 21) = 0.03, p= 0.97). Bongaka le bona ha boa ka ba ba le tšusumetso e matla likarolong tse nkang kotsi ho Balloon analogue-kotsi ea ho nka mosebetsi F (2, 21) = 0.2, p= 0.98; bolela lipompo tse fetotsoeng karolelano: SD: OFF 37.6 ± 11.4ms; LD 38.1 ± 14.4ms; DA 38.8 ± 10.8ms.

Ts'ebetso e Ts'usumetso ea Likarabo

Tlhahiso ea liphetho ka bobeli Liphetoho tse phahameng tsa lets'oa la BOLD ho marang-rang a 'maloa. Keketseho e ile ea bonoa marang-rang a maqhubu a mabeli a pono (motor cortex: x= −18 / 18, y= -93, z= 6 / 0 mm; cerebellum: x= −30 / 30, y= −66 / −57, z= −27 / −21 mm; putamen: x= −21 / 24, y= −3 / 6, z= −3 / 0 mm; tikoloho ea koloi ea maoto: litlhoro: x= −12 / 12,y= 6 / 8, z= 45 / 44 mm; ventral premotor cortex: x= −55 / 45, y= 3 / 6, z= 45 / 36 mm). Menyetla e fumanoe ka "cortex" ea anterior cingex ho genu ea corpus callosum (x= 0,y= 39, z= 0 mm) le "cortex" ea medial pele.x= 0, y= 57, z= 0 mm).

Ha o sheba phello ea meriana, phello e kholo phetohelong e hlahisitsoeng ke BOLD-sign e fumanoe feela ka letsohong le letšehali la orbitofrontal cortex (OFC) (Lethathamo 1). T-Liteko li bonts'itse hore lets'oao la BOLD le tloaelehileng kamora liphetho le ne le phahame boemong ba DA ho feta maemong a LD kapa a OFF (Lethathamo 1). Tlhahlobisong ea covariance, boemo ba DA bo matlafalitse haholo khokahano e nepahetseng lipakeng tsa palo e lekanyelitsoeng ea lipompo tse fetotsoeng le liphetoho tse hlakileng tse hlahisitsoeng ke BOLD-sign ka morao ka letsohong le letšehali la OFC (Lethathamo 1).

Lethathamo 1 

Kameho ea Pramipexole (DA) mabapi le ts'ebetso ea phetisetso ea Feedback

Moputso Ho sebetsa

Kamano e matla e amanang le litekanyetso tsa boleng ba RPE e ile ea fumanoa libakeng tsa sepheo sa mantlha sa mesolimbic dopaminergic system (Setšoantšo sa 2a le b; Lethathamo 2). Ka har'a ventral striatum, meriana ka bobeli ea dopaminergic (LD / DA) e fokotse ts'ebetso ea moputso oa lehae ka tsela e tšoanang ha e bapisoa le OFF (Setšoantšo sa 3a le b; Lethathamo 2). Ho OFC, leha ho le joalo, ke li-DA feela tse fokotsitseng tšebetso ea moputso oa lehae haholo (Setšoantšo sa 3c le d; Lethathamo 2). Tlhahlobo ea covariance e nang le lintlha tse nkang likotsi sebakeng se ikhethileng e bonts'a hore boemo ba DA bo matlafalitse khokahano e mpe lipakeng tsa palo e lekanyelitsoeng ea lipompo tse fetotsoeng le ts'ebetso ea meputso ea lehae ka morao ho lefapha le latelang la OFC (Lethathamo 2).

Setšoantšo sa 2 

Ho lokisa moputso ntle le meriana (TSOHLE). (a) Mohlala oa kamano pakeng tsa karabelo e BONAHALANG nakong ea sephetho le phoso ea ho bolela moputso (RPE) litekanyetsong tsa taba e le 'ngoe. (b) Tlhahlobo ea sehlopha: khokahano e nepahetseng ea maikutlo ...
Setšoantšo sa 3 

Kameho ea meriana ea dopaminergic mabapi le ts'ebetso ea moputso. (a) Likhakanyo tsa phapang le 90% nako ea ho ikhopotsoa le litekanyetso tse boletsoeng esale pele tsa moputso (RPE) ho "ventral striatum"x= -9,y= 21, z= −6 mm). TSOHLE, ntle le dopaminergic ...
Lethathamo 2 

Kameho ea phekolo ea Dopaminergic on Reward Processing

Ho nka liphumano ka bobeli tsa OFC mmoho-ho khothalelitsoe karabelo kamora ho araba le ho hlakola tumellano le boleng ba RPE-motho a ka fihlela qeto ea hore kholo ea kholo e amanang le DA ts'ebetsong ea OFC e itšetlehile ka boleng ba RPE. Litekong tse nang le boleng bo bobe ba RPE, li-DA li kanna tsa eketsa ts'ebetso ea OFC ka tekanyo e kholo ho feta litekong tse nang le boleng bo nepahetseng ba RPE. Ho netefatsa khopolo ena, re boetse re fuputse likarabo tse hlahisang sephetho mabapi le boleng ba RPE ka mokhoa oa mekhahlelo. Leha ho le joalo, ha likhokahanyo tsa phapang e kholo ka ho fetisisa lipapisong ka bobeli li sa ka tsa feta ka botlalo (ts'usumetso e hlahisitsoeng ke sephetho: z= −18; ts'ebetso ea moputso: z= −3), re nts'itse lintlha tsa bohlokoa holima sebaka sa 10mm, se lipakeng tsa maxima a mabeli (x= -24, y= 42, z= −10). E amanang le OFF, DA e ekelitse ts'ebetso ea orbitofrontal ka kotloloho litekong tse nang le boleng bo bobe ba RPE (Setšoantšo sa 4).

Setšoantšo sa 4 

Ho bolela phetoho ea BOLD-sign ho mokokotlo oa morao oa orbitofrontal cortex (10mm sphere e thehiloe ho x= -24,y= 42, z= −10) kamanong le ho putsa boleng ba ho bolela ntle le meriana (OFF) le kamora pramipexole (DA). E amanang le OFF, DA ka kotloloho ...

TŠOHLOA

Phello e ka sehloohong ea boithuto ba rona ke hore ts'usumetso ea tonic dopaminergic le DAs ho bakuli ba PD e fokotse ts'ebetso ea moputso kahare ho OFC ka ts'ebetso e ntseng e eketseha nakong ea liphoso tse mpe tsa ho bolela moputso. Ho tsebo ea rona, sena se emela bopaki ba pele bo matla ba hore li-DA li ka tlosa matlafatso e mpe lithutong tse thehiloeng karabo ka ho thibela ho fokotseha hoa phasic mosebetsing oa synaptic o etsahalang ka liphoso tse mpe tsa ho bolela moputso. Ka bomalimabe, ho fumana hona e ne e le sethethefatsi ka kotloloho, joalo ka ha se sa ka sa bonoa kamora taolo ea LD-eo ho lumeloang hore e ntlafatsa tshusumetso ea li-receptor tsa dopaminergic. Khopolo ena e lumellana le kotsi e eketsehang e ikhethang ea ho nts'etsapele bakuli ba PD ba tšoaroang ke DA (; ; ).

Pono ea rona e tsamaellana le mehlala ea morao-rao ea theoretical le datha ea maiketsetso ea thuto ea ho matlafatsa e thehiloeng ho dopamine (, ; ). Bakuli ba PD ba sa ngolisoang ba bonts'a thuto e sa thekeseleng ea maikutlo mabapi le mesebetsi e fapaneng (; ; ). Leha liphuputso tse ling li supa hore bakuli ba sa hlophisehang ba kanna ba holofala ka ho khetheha ho ithuteng karabo e ntle (; ), Bopaki bo susumetsang ba phello e mpe ea kalafo ea dopamine ho ithuta ka maikutlo a mabe bo bonahala bo lumellana haholoanyane (; ). Ho latela mohlala oa khomphutha o khothalelitsoeng ke Frank le basebetsi-mmoho, ho phatloha ho hoholo ha dopamine kamora meputso e sa lebelloang ho hlahisa litholoana tse matlafatsang ka ho susumetsa li-receptors tsa D1 (). Ka lehlakoreng le leng, likotlo tse sa lebelloang kapa meputso e haneloang e lebisa ho matlafatsong e mpe ka ho fokotsa nako le nako ho saena hoa D2. Ho hlohlella hoa tonic receptor — joalo ka meriana ea DA — ka hona ho ka ntlafatsa litlamorao tsa D1 (mohlala, ho matlafatsa ka matla). Ka lehlakoreng le leng, e ka thibela likhefu ho ho saena ha D2 mme ka ho sitisa ho ithuta hampe. Liphetho tsa rona li supa phello e kholo ea morao, e ka hlalosoang ke D2 / D3 selectivity ea pramipexole (). Ebile, ts'ebetso e hlahisitsoeng ke sepheo sa OFC e ne e phahame le DA mme phello e matlafala e bonahala e le kholo bakeng sa tahlehelo e sa lebelloang ho feta meputso e sa lebelloang, ka hona e fokotsa ho hokahana le litekanyetso tsa RPE. Leha ho le joalo, taba ea hore paradigm ea rona e fapane le e sebelisitsoeng lithutong tsa Frank le basebetsi-mmoho ba ts'ebetso e emela lehae la bohlokoa (, ). Ntle le moo, mohopolo o mong oa khopolo-taba ke oa hore tšusumetso ea tonic ea presynaptic autoreceptors e ka fokotsa ho ikamahanya le litekanyetso tsa RPE ka ho hatella ho thunya ha li-neuron tsa midbrain dopaminergic.

Liphetho tsa rona li supa tokisetsong e lekanang ea ts'ebetso ea moputso ho bakuli ba sa ngolisoang PD, athe LD le DA ka bobeli li fokotse ts'ebetso ea meputso ho ventral striatum le OFC. Sena se tiisa pono ea hore ka kalafo ea ho khutlisa dopamine, ho khutlisetsa maemo a dopamine karolong ea motor ea striatum (dorsal putamen) e kanna ea tla ka tšebeliso e mpe ea ho fetoloa hoa likarolo tse ling tsa kelello (dorso-medial caudate) le li-limbic (ventral striatum, nucleus accumbens) (; ; ).

Na ts'ebetso ea neuronal pele sephetho se ka susumetsa ts'ebetso ea neuronal ea boleng ba RPE metseng e fapaneng ea meriana? Lithutong tse nyane tse phetseng hantle, motho o ne a ka lebella kamano ea liketsahalo tsa nakoana nakong ea ho lebella le ho putsa boleng ba ponelo-pele. Re lokela ho hlokomela, leha ho le joalo, hore phello ena e tebile haholo ho feta kamano le RPE (). Ka tlhahlobo ea tlhaiso-leseling ea data ea rona, ha rea ​​ka ra fumana kamano e joalo maemong afe kapa afe a meriana (OFF, LD, DA). Ebile, motho a ke ke a nahana hore kamano ena e bolokiloe ho PD. Phuputso ea morao-rao e entsoeng morao tjena ho bakuli ba PD kamora ho khaotsa ho sebelisa meriana, taolo ea batho ba baholo le ba banyenyane e bonts'a hore leha ts'ebetso ea RPE e bonahala e bolokiloe hantle, bakuli ba PD le taolo ea batho ba tsofetseng ba bonts'a letšoao le bonts'itseng la tefo ea moputso pele (). Ha re latela sebopeho se poteletseng sa kamano ena ho barupeluoa ba banyane, tahlehelo e atamelaneng ea kamano ena ho bakuli ba tsofetseng le ba PD, le ho haella ha kamano e joalo thutong ea rona, re nahana hore tšusumetso e mpe e ka ba ngata haholo.

Boithuto bona bo ka ba le litlamorao tsa bohlokoa bakeng sa batsomi ba li-pathological ntle le PD. o fumane hore phapang ea ts'ebetso ea "ventral striatal activation" ka mor'a hore e be ntle vskarabelo e mpe ea lichelete e ile ea fokotseha ho barekisi ba methapo ea methapo ba amanang le taolo e ntle. Joalo ka ha bangoli ba boletse, e ntse e tlameha ho hlakisoa, hore na ho fumanwa ho hoholo ho tsoa ho karabelo e sa utloahaleng ho isa ho leruo, kapa ho tsoa likarabo tse makatsang tsa tahlehelo. Seo re se fumaneng se hlahisa potso ea hore na PG e ka amahanngoa le bokhoni bo sa lekaneng ba OFC ho tataisa boits'oaro ha e tobane le litlamorao tse mpe.

Joalokaha ho boletsoe kenyelletsong, ho na le mabaka a mabeli a sehlooho a ho bapisa seo re se fumaneng le ba lemaletseng lithethefatsi. Taba ea pele, mekhoa ea hona joale ea tlhahlobo ea PG le bokhoba ba lithethefatsi tse ngata (). Taba ea bobeli, lithuto tse 'maloa tsa morao-rao tse sebelisang tšebeliso ea lithethefatsi hampe li hatisitse karolo ea bohlokoa ea mesolimbic dopaminergic pathways (; ; ). Ho tšebeliso ea litekanyetso, boleng bo hlahisoang ke liketsahalo kapa mekhoa e itseng e bonahala e fetotsoe (; ; ). Ho na le bopaki bo bongata ba hore OFC e buisana le boleng ba boleng bo tlase 'me ke karolo ea bohlokoa ho etseng liqeto tse lumellanang (; ;; ; ). Ho joalo, boithuto ba morao-rao ba basebelisi ba koae ba netefalitse ho kenya letsoho ha laterC OFC ka ho hloka tšebeliso ea boleng ba maikutlo (). Bafani ba taolo ba ne ba nka moputso o phahameng ho feta ho hapa moputso o tlase, athe ba fetang halofo ea lithuto tse lemalloang ke koae ba ne ba nka moputso ka ho lekana. Phumano ena e ne e hokahane haholo le ts'ebetso e phahameng, e sa amaneloang le chelete ho AFC ea morao-rao. Liphetho tsa rona li fana ka maikutlo a hore bakuli ba li-PD ho bakuli ba PD ba fetisetsa tšebetsong e phahameng ka ho fetesisa ntle le tlhaiso-leseling ka mor'a ho fana ka maikutlo a lichelete - sepheo se ts'oanang se ts'oanang le se hlahisoang ke bokhoba ba koae.

Le ha litlamorao tse tsamaeang le DA mosebetsing oa kamoso oa OFC li ne li amana le liphetoho tse ka behang molemong oa ts'ebetso e kantle ho marang-rang, tsamaiso ea pramipexole e ne e sena tšusumetso e tobileng ea boits'oaro, e pheta liphetho tsa pejana ho baithaopi ba phetseng hantle ba bacha (). Ka mantsoe a mang, litlamorao tsa neuronal tsa DAs li kanna tsa se be matla hoo li ka fetolang boitšoaro ho motho e mong le e mong. Empa ho etsahalang, haeba ts'ebetso ena ea lithethefatsi e sebetsana le tlokotsing ea motho ka mong? Phokotso ea phokotso ea li-receptor tsa DriNUMX tsa striatal ke mokhoa o amanang le tšebeliso ea lithethefatsi (). Ho khahlisang, haufinyane tjena re fumane hore phokotseho e fumanehang ea li-receptor tsa D2 e boetse e khetholla bakuli ba PD ba nang le PG ho bakuli ba PD ntle le PG (). E mong a ka nahana hore bathong ba nang le khatello ea methapo ea D2 e fokotsitsoeng, ho kena-kenana ha li-DA tse nang le D2-mediated-feedback e mpe ea ho ithuta ho ka ntlafatsoa. Leha ho le joalo, motho a ke ke a hlakisa hore tlokotsi eo motho ka mong a nang le eona ea ho ntlafatsa bokhoba ba boitshwaro le eona e hlaha ho tsoa litsamaisong tse sa amaneng le mesolimbic dopamine. Ha ho na mosebetsi o kantle (ke hore, ts'ebetso ea boko e feto-fetohang ka bolokolohi), bakuli ba PD ba nang le matšoao a boima a PG ka nako ea ho ithuta ba bontšitse ho eketseha ha boko maemong a dopaminergic mesolimbic, empa hape le ts'ebetsong, hippocampus, le amygdala (). Ho hlokahala lithuto tse ling sebakeng sena ho khetholla litšobotsi tse bolelang kotsi ea ho ba kotsing ea mokhoa o sa tloaelehang oa neurobehaeveal tse ka hlahisang hang hoba PG e kopane joalo ka boitšoaro.

Ka kakaretso, re fana ka bopaki ba hore ts'usumetso ea tonic ea li-receptor tsa dopamine ea ka pele e ka sitisa tlhahiso ea boleng ba mmele ka ho thibela ho fokotseha hoa ts'ebetso ea cortical synaptic e etsahalang ka karabelo e mpe. Seo re se fumaneng se hlahisa potso, hore na ebe PG e ka 'na ea hlaha ka lebaka la bokhoni ba OFC bo sa sebetseng ba ho tataisa boits'oaro ha e tobane le litlamorao tse mpe.

Leha ho le joalo, ho na le meeli e 'maloa ea lithuto tsa rona e ka hanang sephetho sa rona. Taba ea pele, ha re fumana hore liphuputso tse ithutoang tsa rona li emetse mokhoa o tšoanang oa meriana, e ka se be oona feela sesosa sa PG ho bakuli ba tlokotsing ba nang le PD. Taba ea bobeli, ka fMRI, re ile ra lekanya phetoho ho oxygenation ea mali. Le ha hona ho ka sebetsa e le index ea mesebetsi ea synaptic, thuto ena ha e fuputse li-receptor tsa dopamine ka kotloloho (mohlala ka tšebeliso ea li-radioligands tse lebisang li-dopamine receptors) ka hona, re ke ke ra fihlela qeto efe kapa efe e mabapi le li-neurotransmitters tse amehang. Taba ea boraro, re fuputse tšebetso e ikemetseng ea karabo ea tšebetso. Leha re ile ra khona ho hokahanya liphumano ka kotloloho le likotsi tse behang bophelo kotsing kotsing, ha re a ka ra bokella bopaki bo bong bo hlakileng ba bohlokoa ba boitšoaro ba ho se sebetse ha DAC ka lebaka la ho se sebetse. Meeli e meng ke boholo bo bonyane ba sampole le kotsi ea likamano tse chitja le mehato e ka bang e sa itšetleheng ka motho (). Boithuto ba nako e tlang bo ka khona ho hlakisa karolo ea phetiso ea dopaminergic ea pele ho thuto e mpe ea tlhaiso le ho hlahloba ho se ts'oenyehe ha meriana le DAs kapa bofokoli bo itseng ho bataki ba methapo ea methapo.

lumela hore baa fokola

Re leboha basebeletsi ba lefapha la ho nahana ka bongaka (haholo-holo Adrian Crawley) le setsi sa mathata sa Movement (haholo Rosalind Chuang, MD le Thomas Steeves, MD) ba Sepetlele sa Toronto Bophirima ka thuso ea bona ho etsa thuto. Mosebetsi ona o ne o tšehelitsoe ka nepo ke thuso e tsoang ho Canadian Institutes of Health Research (MOP-64423 to APS) le Safra Foundation. APS e ts'ehetsoa ke Mokhatlo oa Canada oa Patlisiso ea Bophelo bo botle oa lipatlisiso.

Mongolo o botlaaseng ba leqephe

 

TLHOKOMELISO:

Bangoli ba phatlalatsa hore ha ho na likhohlano tsa thahasello.

 

References

  • Ahmed SH, Kenny PJ, Koob GF, Markou A. Bopaki ba Neurobiological ba hedonic allostasis e amanang le ts'ebeliso e ntseng e eketseha ea k'hok'heine. Nat Neurosci. 2002; 5: 625-626. [E fetotsoe]
  • Mokhatlo oa Amerika oa mafu a kelello. Buka ea Tlhatlhobo le Lipalopalo tsa Mathata a Kelello. Mokhatlo oa Amerika oa mafu a kelello; Washington, DC: 1994.
  • Bayer HM, Lau B, Glimcher PW. Lipalo-palo tsa literene tsa midbrain dopamine neuron spike litleneng tse tsohileng. J Neurophysiol. 2007; 98: 1428-1439. [E fetotsoe]
  • Breiter HC, Aharon I, Kahneman D, Dale A, Shizgal P. Litšoantšo tse sebetsang tsa likarabo tsa methapo ho tebello le boiphihlelo ba leruo le tahlehelo ea lichelete. 2001; 30: 619-639. [E fetotsoe]
  • Cilia R, Siri C, Marotta G, Isaias IU, De Gaspari D, Canesi M le ba bang. Ts'ebetso e sa tloaelehang e sebetsanang le ho becha hoa lefu la Parkinson. Arch Neurol. 2008; 65: 1604-1611. [E fetotsoe]
  • Cools R.Dopaminergic modulation ea ts'ebetso ea ts'ebetso ea kelello-e amang kalafo ea L-DOPA ho lefu la Parkinson. Moruti Neurosci Biobehav Rev. 2006; 30: 1-23. [E fetotsoe]
  • Pholiso R, Altamirano L, D'Esposito M. Ho ithuta ka phetoho ho lefu la Parkinson ho latela maemo a meriana le valence ea sephetho. Neuropsychologia. 2006; 44: 1663-1673. [E fetotsoe]
  • Lits'oants'o tsa R, Barker RA, Sahakian BJ, Robbins TW. Ts'ebetso e ntlafalitsoeng kapa e sa sebetseng ea ts'oaetso ea lefu la Parkinson e le ts'ebetso ea meriana ea dopaminergic le litlhoko tsa mosebetsi. Cereb Cortex. 2001; 11: 1136-1143. [E fetotsoe]
  • Mokhanni-Dunckley E, Samanta J, Stacy M. Pathological papali ea chelete e amanang le kalafo ea dopamine agonist lefung la Parkinson. Neurology. 2003; 61: 422-423. [E fetotsoe]
  • Elliott R, Newman JL, Longe OA, Deakin JF. Mefuta e fapaneng ea karabelo ho striatum le orbitofrontal cortex ho moputso oa lichelete ho batho: thuto ea parametric e sebetsang ea matla a khoheli. J Neurosci. 2003; 23: 303-307. [E fetotsoe]
  • Frank MJ, Samanta J, Moustafa AA, Sherman SJ. Tšoara lipere tsa hau: ho se ts'oenyehe, ho hlasimoloha ho tebileng ha boko, le meriana ho Parkinsonism. Saense. 2007; 318: 1309-1312. [E fetotsoe]
  • Frank MJ, Seeberger LC, O'Reilly RC. Ka rantipole kapa ka thupa: ho matlafatsa tsebo ea ho ithuta ho Parkinsonism. Saense. 2004; 306: 1940-1943. [E fetotsoe]
  • Friston KJ, CD ea Frith, Turner R, Frackowiak RS. Ho khetholla hemodynamics e hlahisitsoeng ke fMRI. Nako ea bophelo. 1995; 2: 157-165. [E fetotsoe]
  • Galpern WR, Stacy M. Tsamaiso ea mathata a ho laola maikutlo ho lefu la Parkinson. Likhetho tsa Therr Ther Ther. 2007; 9: 189-197. [E fetotsoe]
  • Garavan H, Pankiewicz J, Palesa A, Cho JK, Sperry L, Ross TJ, et al. Takatso ea cocaine e bakoang ke cue: neuroanatomical e ikhethang bakeng sa basebelisi ba lithethefatsi le ts'usumetso ea lithethefatsi. Ke J Psychiatry. 2000; 157: 1789-1798. [E fetotsoe]
  • Genovese CR, Lazar NA, Nichols T. Ho boloka limmapa tsa lipalo ka mokhoa o sebetsang oa neuroimaging ho sebelisa sekhahla sa ho sibolla ho fosahetseng. Nako ea bophelo. 2002; 15: 870-878. [E fetotsoe]
  • Goldstein RZ, Tomasi D, Alia-Klein N, Cottone LA, Zhang L, Telang F, le al. Kutloisiso e ikhethang ea likarolo tsa chelete e amahanngoa le ts'ebetso ea frontolimbic ho putsa batho ba hlekefetsang k'hok'heine. Ho Tšepa Joala ba Lithethefatsi. 2007; 87: 233-240. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
  • Grigson PS, Twining RC. Phepelo e bakoang ke cocoa ea ho ja saccharin: mohlala oa ho theola lithethefatsi ka lebaka la litlhohonolofatso tsa tlhaho. Behav Neurosci. 2002; 116: 321-333. [E fetotsoe]
  • Hamidovic A, Kang UJ, de Wit H. Litlamorao tsa tekanyetso e tlase ho isa ho e itekanetseng ea pramipexole mabapi le ho se ts'oenyehe le ho tseba baithaopi ba phetseng hantle. Kliniki ea Psychopharmacol. 2008; 28: 45-51. [E fetotsoe]
  • Hollerman JR, Tremblay L, Schultz W. Tšusumetso ea tebello ea moputso mesebetsing e amanang le boits'oaro e amanang le boits'oaro ho primate striatum. J Neurophysiol. 1998; 80: 947-963. [E fetotsoe]
  • Knutson B, Fong GW, Adams CM, Varner JL, Hommer D. Ho ikarola ha tebello ea moputso le sephetho ka fMRI e amanang le ketsahalo. Ts'ebetso. 2001; 12: 3683-3687. [E fetotsoe]
  • Knutson B, Westdorp A, Kaiser E, Hommer D. FMRI ponahalo ea ts'ebetso ea boko nakong ea ts'ebetso ea tšusumetso ea chelete. Nako ea bophelo. 2000; 12: 20-27.E fetotsoe]
  • Kriegeskorte N, Simmons WK, Bellgowan PS, Baker CI. Tlhahlobo ea selikalikoe ho li-neuroscience tsa sistimi: likotsi tsa ho ina habeli Nat Neurosci. 2009; 12: 535-540. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
  • Lejuez CW, Bala JP, Kahler CW, Richards JB, Ramsey SE, Stuart GL, et al. Tlhatlhobo ea boits'oaro ba ho ipeha kotsing: Balloon Analogue Risk Task (BART) J Exp Psychol Appl. 2002; 8: 75-84. [E fetotsoe]
  • O'Doherty JP, Dayan P, Friston K, Critchley H, Dolan RJ. Mefuta ea phapang ea nakoana le thuto e amanang le moputso bokong ba motho. Neuron. 2003; 38: 329–337. [E fetotsoe]
  • Potenza MN. Hlahloba. Neurobiology ea papali ea chelete ea papali ea chelete le ho lemalla lithethefatsi: kakaretso le liphetho tse ncha. Philos Trans R Soc Lond B Biol Sci. 2008; 363: 3181-3189. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
  • Pontone G, Williams JR, Bassett SS, Marsh L. Likarolo tsa bongaka tse amanang le mathata a ho laola maikutlo ho lefu la Parkinson. Neurology. 2006; 67: 1258–1261. [E fetotsoe]
  • Ragonese P, Salemi G, Morgante L, Aridon P, Epifanio A, Buffa D, le al. Boithuto ba taolo ea linyeoe ka koae, joala le tšebeliso ea kofi pele ho lefu la Parkinson. Neuroepidemiology. 2003; 22: 297-304. [E fetotsoe]
  • Reuter J, Raedler T, Rose M, Hand I, Glascher J, Buchel C. Papali ea papali ea chelete e hokahane le ho fokotsa ts'ebetso ea ts'ebetso ea moputso oa mesolimbic. Nat Neurosci. 2005; 8: 147-148. [E fetotsoe]
  • Schott BH, Niehaus L, Wittmann BC, Schutze H, Seidenbecher CI, Heinze HJ, le al. Boloetse ba Parkinson ba botsofali le ba pele-pele bo ama mekhoa e arohaneng ea neural ea ts'ebetso ea moputso oa mesolimbic. Boko. 2007; 130: 2412-2424. [E fetotsoe]
  • Schultz W. Ho etsa semmuso ka dopamine le moputso. Neuron. 2002; 36: 241-263. [E fetotsoe]
  • Seedat S, Kesler S, DJ ea Niehaus, DJ oa Stein. Boitšoaro ba papali ea chelete ea ho becha: Ho hlaha kamora ho kalafo ea lefu la Parkinson le baemeli ba dopaminergic. Tšoenyeha ho Tepella Maikutlong. 2000; 11: 185-186. [E fetotsoe]
  • Matla a kalafo a Seeman P. Anti-Parkinson a tsamaellana le lihlahisoa tsa bona ho li-receptor tsa dopamine D2 (High). Synapse. 2007; 61: 1013-1018. [E fetotsoe]
  • Shohamy D, Myers CE, Grossman S, Sage J, Gluck MA, Poldrack RA. Menehelo ea Cortico-striatal ho thuto e ipapisitseng le maikutlo: ho fetola lintlha ho tsoa ho neuroimaging le neuropsychology. Boko. 2004; 127: 851-859. [E fetotsoe]
  • Litepisi TDL, Miyasaki J, Zurowski M, Lang AE, Pellecchia G, van Eimeren T, et al. Ho lokolloa ha dopamine ea ventral striatal ho bakuli ba lefu la Parkinson ba nang le papali ea chelete ea mafu: thuto ea [11C] raclopride PET. Boko. 2009; 132: 1376-1385. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
  • Sutton RS, Barto AG. Matlafatso ea ho Ithuta: Selelekela. MIT Tobetsa; Cambridge, MA: 1998.
  • Swainson R, Rogers RD, Sahakian BJ, Summers BA, Polkey CE, Robbins TW. Ho ithuta ka mokhoa o ikhethileng le ho fokotsa likhaello ho bakuli ba nang le lefu la Parkinson kapa liso tse ka pele kapa tsa nakoana tsa lobe: litlamorao tse ka bang teng tsa meriana ea dopaminergic. Neuropsychologia. 2000; 38: 596-612. [E fetotsoe]
  • Tomer R, Aharon-Peretz J. Ho tsebahala ka ho batla le ho qoba kotsi ho lefu la Parkinson: litlamorao tsa khaello ea asymmetric dopamine. J Neurol Neurosurg Psychiatry. 2004; 75: 972-975. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
  • Tremblay L, Schultz W. Likhetho tse amanang le moputso ho primate orbitofrontal cortex. Tlhaho. 1999; 398: 704-708. [E fetotsoe]
  • Valentin VV, Dickinson A, O'Doherty JP. Ho tseba likaroloana tsa thuto e tataisitsoeng ka sepheo bokong ba motho. J Neurosci. 2007; 27: 4019-4026. [E fetotsoe]
  • Volkow ND, Fowler JS, Wang GJ. Boko ba motho bo lemaletseng bo talingoa ho latela lithuto tsa litšoantšo: lipotoloho tsa boko le maano a kalafo. Neuropharmacology. 2004; 47 (Tlatsetso ea 1): 3-13. [E fetotsoe]
  • Volkow ND, Fowler JS, Wang GJ, Baler R, Telang F. Ho nka karolo ea dopamine ts'ebetsong ea lithethefatsi le bokhoba ba lithethefatsi. Neuropharmacology. 2009; 56 (Tlatsetso ea 1): 3-8. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
  • Volkow ND, Wang GJ, Fowler JS, Logan J, Gatley SJ, Hitzemann R, le al. Ho fokotsa boikarabello ba striatal dopaminergic boikarabellong ba lithuto tse itšetlehileng ka k'hok'heine. Tlhaho. 1997; 386: 830-833. [E fetotsoe]
  • Voon V, Hassan K, Zurowski M, Duff-Canning S, ea Souza M, Fox S, le al. Ho ata ha monyetla oa papali ea papali ea chelete le mokhatlo oa meriana lefung la Parkinson. Neurology. 2006; 66: 1750-1752. [E fetotsoe]
  • Waelti P, Dickinson A, Schultz W. Dopamine likarabo li latela likhopolo tsa mantlha tsa thuto ea semmuso ea thuto. Tlhaho. 2001; 412: 43-48. [E fetotsoe]
  • Weintraub D, Koester J, Potenza MN, Siderowf AD, Stacy MA, Whetteckey J, et al. bakeng sa Sehlopha sa Boithuto ba DOMINION. Tlhatlhobo ea Domapinergic le Mathata a Taolo ea Ts'usumetso ho Ditsapo tsa Parkinson: Liphetho tsa mantlha tsa thuto ea sefapano ea bakuli ba fetang bakuli ba 3,000. 12th International Congress ea Maloetse a Ts'oaetso ea Parkinson le Phallo ea Motsamaisi; Chicago, IL. 2008.2008.
  • White TL, Lejuez CW, de Wit H. Liteko tsa tlhahlobo ea liteko tsa Balloon Analogue Risk Task (BART) Exp Clin Psychopharmacol. 2008; 16: 565-570. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
  • Yacubian J, Glascher J, Schroeder K, Sommer T, Braus DF, Buchel C. Disistimi tse ka arohanang bakeng sa likhakanyo tsa phaello le tahlehelo le liphoso tsa ponelopele bokong ba motho. J Neurosci. 2006; 26: 9530-9537. [E fetotsoe]