Lintho tse fapaneng le ho fumanoa ha D2 dopamine receptor le ho itšetleha ka mokhoa o sa tloaelehang litlamong tsa banna tse phelang nakong ea ha li se li le cocaine (2010)

LIPOTSO: E bontša hore liphoofolo tse hlahelletseng li na le li-receptor tsa D2 tse phahameng, 'me li nka nako e telele pele li etsa lipatlisiso ka ntho e ncha e kentsoeng terakeng ea tsona. Ho batho, borena bo fetolela ho ikutloa bo monate ka uena le bophelo ba hau. Ho hoheloa ke bocha ha ho bolele hore u ka ba lekhoba le ho ikutloa u khotsofetse ka seo u nang le sona.


Psychopharmacology (Berl). 2010 Mar;208(4):585-92. doi: 10.1007/s00213-009-1756-4.

Czoty PW1, Gage HD, Nader MA.

inahaneloang

Tlhaloso

Boithuto ho litšoene tse bolokiloeng sechabeng ho bonts'itse tšusumetso ea boemo ba maemo a phahameng sechabeng ho li-dopamine DeptNUMX receptors le litlamorao tse matlafatsang tsa koae e phatlohang kamora ho itaola ka nako e telele.

sepheo

Morero oa thuto e ne e le ho hlahloba litlamorao tsa ho ila koae ho li-receptor tsa D2 ho litšoene tse bolokiloeng sechabeng le ho holisa litšobotsi tsa boits'oaro mehatong ea ho boela nthong e ncha.

Lisebelisoa le mekhoa

Ho sebelisitsoe litšoene tse leshome le metso e 'meli tsa lelapa tse tona tse nang le bophelo bo botle tse nang le boiphihlelo tse ngata tsa ho ikoetlisetsa cocaine (boiphihlelo bo tloaelehileng ba bophelo ~ 270 le 215 mg / kg bakeng sa litšoene tse hlaheletseng le tse tlase. Ho tlohela mosebetsi ho ile ha nka likhoeli tse ka bang 8, kamora moo ho fumaneha ha D2 receptor ho hlahang ho sebelisoa positron emission tomography le D2 ligand [18F] fluoroclebopride. Boitšoaro bo mabapi le bocha bo ile ba hlahlojoa hape lithutong tsena hammoho le litšoene tse robong tse nang le matlo a fapaneng.

Results

Nakong ea thibelo, ho fumaneha ha li-D2 sebakeng sa caudate ho ne ho phahame haholo ho feta litšoene tse tlasa lefatše. Karolelano ea ho ts'oara ntho e ncha e ne e boetse e phahame haholo ho litšoene tse kholo ha li bapisoa le ba ka tlasa lefatše kapa litšoene tse nang le matlo ka bomong. Ho litšoene tse nang le boiphihlelo sechabeng, ho ile ha bonoa khokahano e ntle ea lipakeng tsa caudate nucleus D2 receptor le latency ea ho ama ntho e ncha.

Nahanisisa

Le ha tsamaiso ea cocaine e sa foleng e hlakisa bokhoni ba taolo ea sechaba ho fetola ho fumaneha ha D2 le kutloelo-pele ho litlamorao tse matlafatsang tsa koae, ts'usumetso ena e nahanisisa hape nakong ea ho khaotsa ho tsuba. Ntle le moo, datha e fana ka maikutlo a hore boiphihlelo ba nakong e fetileng bo nang le taolo ea sechaba bo ka lebisa ho pheletsong e telele ho hanyetsanang le bocha — tšobotsi e amanang le ho ba kotsing ea tlhekefetso ea koae.

Keywords: Maemo a maemo a bophelo, Ho amohela litaba tsa bocha, PET imaging, Vulnerability, li-primates tse se nang botho

Pejana mosebetsi libakeng tsa boiketlo ba batho tse seng tsa botho o fumane hore dopamine (DA) D2 receptor fumaneha, joalo ka ha e lekotsoe ka positron emission tomography (PET), e ne e phahame ho litšoene tse kholo ha li bapisoa le liphoofolo tse tlasa lefatše (Grant et al. 1998; Morgan et al. 2002). Ho e 'ngoe ea lithuto tsena, phumaneho ea li-receptor tsa D2 e eketsehile ka 20% ho litšoene tse fumanoeng matla empa li ne li sa fetohe ho ba ka tlase ho (Morgan et al. 2002). Liphetoho tsena tsa ho fumaneha ha li-D2 tsa receptor li bile le litlamorao tsa boitšoaro ba hore litšoene tse hlahelletseng li ipehetse hantle haholo ha li bapisoa le koae. Kahoo, ho bonahala eka maemo a phahameng a "D2 receptor" a sirelelitse "litšoene tse matla ho tsoa litlamorao tse matlafatsang tsa koae e lumellanang le dintlha ho batho le liphoofolo tsa maele.Volkow et al. 1999; Thanos et al. 2001; Nader et al. 2006; Dalley et al. 2007).

Lithuto tsena li bonts'itse hore maemo a maemong a phahameng sechabeng a ka susumetsa tsietsi ho litlamorao tse matlafatsang tsa koae nakong ea ho pepeseha kapele; Leha ho le joalo, ha ho tsejoe letho ka tšusumetso ea maemo a sechaba ho litšoene tse nang le nalane e matla ea taolo ea koae. Ho litšoene tse tsamaisitsoeng ke sehlopha tse hlalositsoeng kaholimo, liphapang tse amanang le maemo a bophelo sechabeng sa D2 li fumaneha le ho itlhokomela ha koae ha lia ka tsa bonoa hang ha litšoene li na le k'hok'heine ea koae ka lilemo tse 'maloa (Czoty et al. 2004). Kahoo, tšusumetso ea tikoloho ea sechaba e qhalakane ha nako e ntse e ea, ka mokhoa o hlakileng ka lebaka la litlamorao tse sa tobang tsa lithethefatsi tsa koae ho li-receptor tsa D2. Morero oa mantlha oa thuto e teng hona joale e ne e le ho lekola hore na maemo a amanang le boemo ba bophelo sechabeng sa D2 a fumaneha hape ha a ka ts'oaroa ke koae kapa, ka mokhoa o fapaneng, hore na ho pepesoa ha cocaine ka nako e telele ho fetotse ts'ebetso ea kelello joalo ka hore neuroplasticity e amanang le boemo ba maemo a sechaba e ne e se e se khoneha.

Morero o mong oa thuto ena e ne e le ho hlahloba kamano pakeng tsa ho fumaneha ha D2 le mekhoa ea botho ho litšoene tse nang le koae. Boithuto ba pelehi bo thehile khokahano lipakeng tsa botho le ho ba kotsing ea tlhekefetso ea lithethefatsi (Dawe le Loxton 2004; Verdejo-Garcia et al. 2008). Liphoofolong tsa liphoofolo, mehato ea likarolo tse fapaneng tsa ts'usumetso, joalo ka ho ts'oaroa ke bongoana, e ka bolela tlhoko ea maikutlo mabapi le litlamorao tsa boitšoaro bo amanang le tlhekefetso ea psychostimulants (mohlala, Piazza et al. 1989, 2000; Bardo et al. 1996; Perry et al. 2005; Dalley et al. 2007). Ho batla maqhubu a holimo ho kenyellelitsoe le ho fumaneha habonolo ha li-receptor tse tlase tsa D2, maemo a phahameng a kantle ho DA le ho ba kotsing ea taolo ea lithethefatsi (Piazza et al. 1991; Hooks et al. 1991; Rouge-Pont et al. 1993; Dalley et al. 2007). Thutong ea hona joale, re lekotse kamano ea karabelo ea bohlasoa le ho fumaneha ha li-receptor tsa D2 mohaleng oa caudate le putamen ea litšoene tse nang le koae ea koae; latency ea ho ama ntho e ncha e ne e bapisoa le data e tsoang ho litšoene tsa taolo ea cocaine-naïve ka bomong. Ho ipapisitse le kamano lipakeng tsa ho fumaneha ha li-D2 le litekanyetso tsa ho batla ho buoa ka likhoto, re fane ka maikutlo a hore litšoene tse hlahelletseng li ka se sebetse hantle ho feta batho ba ka tlasa (ba re, latency e telele ea ho ama ntho e nyane) le hore phapang e amanang le boemo ba batho sechabeng e tla etsa hore ba fumane lintho tse ncha. phapang e tšoanang ho fumaneheng ha D2 receptor.

Lisebelisoa le mekhoa

Lihlooho

Litšoene tse tona tse mashome a mabeli a motso o mongMacaca fascicularis) e sebelitse e le lithuto. Tse leshome le metso e 'meli tsa litšoene tsena li ne li e-na le nalane ea ho lula ka lihlopha tsa batho ba bararo kapa ba bane lilemo tse fetang 2 (Czoty et al. 2004, 2005b). Qalong ea liteko tsa morao tjena, litšoene tse tšeletseng li ne li lula lihlopheng tse peli tsa setšoene ka sehlopha se le seng, 'me litšoele tse tšeletseng li ne li e-na le ntlo e le' ngoe. 12 kaofela e ne e e-na le matsatsi a 'maloa a sebelisoang ke koae ka matsatsi a fetang a 2 tlasa kemiso e tsitsitseng ea (c) ea tlhahiso ea koae (Czoty et al. 2004) kapa lenane la nako le nako la lijo tsa FR le cocaine (Czoty et al. 2005b). Ho ne ho se na phapang lipakeng tsa nako e telele ea bophelo kapa tlhaselo ea cocaine ea selemo se fetileng lipakeng tsa litšoene tse hlahelletseng le tse tlase, leha e le ea pele e neng e batla e phahame ho litšoene tse hlaheletseng (Lethathamo 1). Litšoene tse robong tse setseng li ne li bolokiloe ka bomong 'me li ne li se na ponaletso ea koae pele. Liphoofolo tsena li ne li kenyellelitsoe e le ho lekola ka botlalo tšusumetso ea matlo a bophelo setulong sa rona sa mantlha sa boits'oaro (reacuction to a novelment). Tšoene e 'ngoe le e' ngoe e ne e kentsoe molala oa nalane (Lihlahisoa tsa Primate, Redwood City, CA, USA) mme e koetliselitsoe ho lula ka khutso setulong se tloaelehileng sa lithibelo (Primate Products) se sebelisa poleiti e entsoeng ka tšepe e se nang sekepe e khomaretsoeng molaleng (Lihlahisoa tsa Primate) . Litšoene li ne li imeloa beke le beke 'me li feptjoa lijo tse lekaneng letsatsi le leng le le leng (Purina Monkey Chow le litholoana le meroho tse ncha) ho boloka boima ba' mele ka hoo e batlang e le 95% ea maemo a mahala a phepo. Boima ba 'mele, bo neng bo lekana le 5.3 kg (SEM, 0.7 kg), ha boa ka ba fetoha haholo nakong ea ho itima lijo' me bo ne bo sa tšoane lipakeng tsa litšoene tse hlaheletseng le tse tlase. Metsi a ne a fumaneha lipapatso ka har'a ntlo ea likhomo.

Lethathamo 1  

Tlhaloso ea nalane ea litšoene tsa cocaine (limiligrama ka kilo), nako ea ho thibela pelehi (matsatsi), le boits'ebetso nakong ea bootsoa, ​​ho latela maemo a sechaba

Litšoene li ne li lula litsing tsa tšepe tse senang litšepe (0.71 × 1.73 × 1.83 m; Allentown Caging Equipment, Co, Allentown, NJ, USA) ka li-partwork tsa wire mesh tse ntšitsoeng tse arotseng litšoene ho ba li-quadrants (0.71 x 0.84 × 0.84 m). Litšoene tse bolokiloeng ka bongata li ne li aroloa letsatsi le leng le le leng ka lihora tse 'maloa nakong ea tšebetso le ho fepa; li-partitions li lula sebakeng sa litšoene tse ikhethileng ka bonngoe. Boiketlo ba sechaba bo ne bo reriloe pejana bakeng sa tšoene e 'ngoe le e' ngoe ho latela sephetho sa liphihlelo tsa kalafo e sebelisang mekhoa e ts'oanang le e hlalositsoeng pele (bona Kaplan et al. 1982; Czoty et al. 2005b, 2009). Ka bokhutšoanyane, bashebelli ba babeli ba ile ba etsa likarolo tse 'maloa tsa ho shebella tsa 15-min ka pente. Boitšoaro bo bobe, bo ikokobelitseng le bo kopanetsoeng bo tlalehiloe ho latela ethogram e hlalositsoeng pele (bona Lethathamo la 1 ho Morgan et al. 2000) sebelisa software ea Noldus Observer (Noldus Information Technology; Wageningen, The Netherlands). Likarolong tsena tsa sehlopha sa boikhathollo, lingoloa tse iqapetsoeng le tse amohelang boitšoaro li tlalehiloe. Tšoene ka pene e 'ngoe le e' ngoe e loantšang batho bohle ebile e ikokobelletsa eona e ne e ngotsoe #1 (e hlahelletseng ka ho fetisisa). Monkey e khethiloeng ka tlaasana e bontšitse boits'oaro bo bobe bo tlase mme e romelloa ho litšoene tse ling kaofela ka pene. Ka pene e 'ngoe le e' ngoe ea litšoene tse tharo, tšoene e # 2 e maemong a holimo e ikokobelletsa tšoele e tona e kholo ka ho fetisisa 'me e hlaseloa ho monkey e ka tlaase ho fetisisa; ka hona, lirafshoa tse lipenseng tse neng li entsoe ka litšoene tse tharo li ne li le mola ebile li le lipuisano. Bakeng sa lithuto tsa hona joale, litšoene tsa # 1 tse behiloeng maemong a phahameng li ne li nkuoa li le matla (n= 5), le litšoene tse ling kaofela li ne li nkuoa li le tlase (n= 7). Bolulo ba liphoofolo le ho sebetsana le litsamaiso tsohle tsa liteko li entsoe ho latela Lekhotla la Naha la Lipatlisiso la 2003 Tataiso bakeng sa Tlhokomelo le Ts'ebeliso ea Limmammali ho Neuroscience le Behahlangual Research mme ba amoheloa ke Komiti ea Tlhokomelo ea Liphoofolo le Ts'ebeliso ea Yunivesithi ea Wake Forest. Tlatsetso ea tikoloho e ile ea fanoa joalo ka ha ho hlalositsoe Lenaneong la Tlhokomelo ea Liphoofolo le Ts'ebeliso ea Univesithi ea Tsoha ea Tlhaho ea Batho ba Tikoloho e seng Batho.

MR le PET imaging

Ho ile ha fumanoa setšoantšo sa bokong ka mokhoa o mong le o mong o tšehelitsoeng ke sechaba se sebelisang matla a tlhaho a tšebeliso ea matla a kelello (Mono). Hoo e ka bang metsotso ea 20 pele ho scan, lithuto li ne li sa anngoe ka ketamine (15 mg / kg, im) ebe li isoa setsing sa MRI. Anesthesia e ile ea bolokoa nakong ea ts'ebetso ea ho sekaseka ka li-supplements tsa ketamine ha ho hlokahala. 3D e senyehileng ea gradient-e hopotsitsoeng e fumanehang litšoantšong tsa bongo ea boemo bo tsitsitseng e ile ea fumanoa (nako ea echo 5, nako ea ho pheta-pheta 45, flip angle 45, bandwidth 15.6 kHz, lebaleng la (FOV) 18 cm, 256 × 192 matrix, slice mm palo ea monyaka oa 2) ka 3-T GE Signa NR scanner (GE Medical Systems). Litšoantšo tsa bokong tse nang le boima ba T1.5 li sebelisitsoe ho hlalosa likarolo tsa mokokotlo (ROI), ho kenyelletsa le radius ea letsoho le letšehali le ho le letshehadi (radius) (1 mm radius), bakeng sa coreg usajili ea morao-rao ka litšoantšo tsa PET. Liphoofolo tse ruiloeng ka bomong li ne li sa ithutoe ka PET.

Nakong ea thibelo, scans ea PET e ne e etsoa ho tšoene e 'ngoe le e' ngoe ho lekola phumano ea D2 receptor e sebelisa radioligand ea D2 [18F] fluoroclebopride (FCP), e sa khetholle pakeng tsa subtypes ea D2-like superfamily (ke hore, D2, D3, le D4 li-receptors; Mach et al. 1996). Nako ea ho ila koaeine e ne e sa fapana haholo lipakeng tsa litšoene tse hlaheletseng le tse tlasa maemo a tlase (Lethathamo 1). Pele ho thuto e 'ngoe le e' ngoe, litšoene li ne li sa anngoe ka 10 mg / kg ketamine mme li isoa Setsing sa PET. Lintlha mabapi le [18F] Kakaretso ea FCP, protocol ea ho fumana data, Pampiri ea mali, le tlhahlobo ea metabolite li hlalositsoe ka botlalo nakong e fetileng (Mach et al. 1993a, b, 1996, 1997; Nader et al. 1999). Ka bokhutšoanyane, e ne e kengoa ka mokhoa o sa tloaelehang le venous catheter ka thupa e poteletseng bakeng sa sampole ea mali le ente ea tracer. Sethala sa paralytic (0.07 mg / kg vecuronium Br, iv) se ile sa tsamaisoa mme moea o kenella ka moea oa phefumoloho ho pholletsa le ScN ea 3-h PET scan. Litekanyetso tse tlatsetsang tsa vecuronium (0.1 mg / h) li ne li fanoa ho pholletsa le thuto. Mocheso oa 'mele o ne o bolokoa ho 40 ° C,' me lipontšo tsa bohlokoa (lebelo la pelo, khatello ea mali, sekhahla sa ho hema, le mocheso) li ile tsa beoa leihlo ho sa sebetsoa letho ka botlalo.

Litšoantšo li fumanoe ho scan nineteete ea General Electric Advance NXi PET. Ka skena e le 'ngoe, Advance NXi e fane ka mela ea 35 e fetohang ka 4.25-mm-to-Center spiding ka holim'a sebaka sa 15.2-cm axial. Tharollo ea transaxial ea scanner e qala ho 3.8 mm bohareng ba FOV ho ea 7.3 mm radial le 5.0 mm tangential ho radius ea 20 cm ha e hlophisoa bocha ka sefofane sa tsela. Tharollo ea eona ea axial e tloha ho 4.0 mm bohareng ho 6.6 mm sebakeng sa 20 cm ha e hlophisoa bocha ka feme ea ramp. Bakeng sa tlhaiso-leseling e batsi ka ts'ebetso ea skena sena sa skena DeGrado et al. (1994). Qalong ea scan, e ka bang 5 mCi ea [18F] FCP e ile ea kenngoa ente, ea lateloa ke 3 ml ea saline ea heparinized. Ho ile ha etsoa liteko 'me litšoantšo tsa ngolisoa ho MRI ea sehlooho ka seng Czoty et al. 2005a). Ho ile ha etsoa li-curve-time-time curve tsa ho tsepamisa mohopolo oa li-radiotracer ho ROI tse hlalositsoeng ho MRI e 'ngoe le e' ngoe e ngolisitsoeng. Distribution volume ratios (DVR) ea motsoako oa caudate le putamen li ile tsa baloa ho sebelisoa cerebellum e le sebaka sa boits'oaro le mokhoa o hlakileng oa Logan et al. (1996). Kahoo, DVR e sebelitse e le index ea tse ikhethang [18F] FCP e tlama ho ROI e 'ngoe le e' ngoe.

Karabo e bolokiloeng ka lijo

Nakong ea ho ila koae, litšoene tse robeli ha lia ka tsa fumana lithethefatsi tse ling. Litšoene tse tharo (C-6528, C-6628, le C-6629) li fumane liente tsa serotonin 1A receptor agonist 8-OH-DPAT (<0.4 mg / kg kakaretso ho feta libeke tse 'maloa) pele ho linako tsa boits'oaro tseo ba ileng ba li araba tlasa kemiso ea nako e tšoanang ea FR ea lijo le letsoai le fumanehang (Czoty et al. 2005b). Ho feta likhoeli tse 'maloa, C-6526 e ne e pepesehetse 4.7 mg / kg ea benzodiazepine midazolam tlasa kemiso ea nako le nako ea lijo le ho fumaneha ha midazolam (lithuto tse sa phatlalatsoang). Bonyane likhoeli tsa 4.5 li fetile kamora ho pepesetsoa hoa lithethefatsi sena pele ho scan ea PET. Nakong eo le bakeng sa nako ea ho itima liphoofolo tsohle, litšoene li ile tsa nka karolo lithutong tsa boits'oaro hang ka beke ka sepheo sa ho boloka boits'ebetso kamora ho khaotsa linako tsa ho itaola. Letsatsi le leng le le leng, litšoene li ne li aroloa ka ho arola likhopo hore e be tse mahareng a mane. Ka mor'a moo, tšoene e 'ngoe le e' ngoe e ne e lutse setulong se thibelang lintho 'me e kenngoa ka kamoreng e kenelletseng hantle e nang le molumo (1.5 × 0.74 × 0.76 m; Nakong ea seboka, likarabo tsa 50 ho lever ea sebetsang (FR50) li hlahisitse tlhahiso ea lijo tsa 1-g. Matsatsi a qetetse ho fihlela li-30 tsa li-reinforcers li se li fumanoe kapa 60 min e felile, ke efe e tlang pele.

Karabo ea bongoaneng

Nakong ea ho khaotsa ho sebelisa koae ho litšoene tse bolokiloeng sechabeng le ho liphoofolo tsohle tse ikemetseng, ho ile ha etsoa qeto ea ho ama ntho e ncha. Taba ea mantlha ke hore, monkey e kantle ho terata e haufi le ntlo ea mokoetlisi e tlositsoe, karohano e tlositsoe lipakeng tsa koaletsoeng, mme taba eo e ile ea isoa terakeng e haufi. Ka mor'a moo, karohano e ile ea nkeloa sebaka 'me ntho ea nalane, lebokose le neng le lekola 30.5 × 20.3 × 20.3 cm le entsoe ka Plexiglas e ntšo, la beoa ka lekarecheng la hae la monkey le se nang letho. Qetellong, karohano eo e ile ea felisoa hape 'me ea hatisoa ke monkey ea ho ama ntho e tlalehiloeng. Haeba monkey e sa ka ea ama ntho e kahare ho 15 min, ho fanoa ka lintlha tsa 900 s. Linako tsohle li ile tsa buloa video 'me tsa bonoa ke bashebelli ba sa boneng boemo ba sechaba sa litšoene. Ha e batla e hanyetsana, nako e phahameng ea 900-s e ne e thehiloe ho data ea pele (A Bennett le P Pierre, e sa phatlalatsoe) mme e thehiloe pele ho qalo ea teko ena.

Tlhahlobo ea lintlha

Li-DVR tse bokong ba caudate le putamen li ne li bapisoa pakeng tsa litšoene tse hlaheletseng le tse tlasana tse sebelisang t liteko. Mabapi le ho nchafatsoa hoa ntho, hobane litšoene tse ling tse hlaheletseng ha lia ka tsa ama ntho e ka har'a 900 s 'me ka hona li fuoe lintlha tsa 900, (nonparametric) Kruskal-Wallis tekolo e le' ngoe ea phapang (ANOVA) e sebelisitsoeng, ea lateloa ke hoc Mann -Whitney U liteko. Kamora nako ea hore litšoene tsena li be le botsoalle, lihokahanyo lipakeng tsa maqhubu a ho ama ntho e ncha le [18F] FCP DVRs in the caudate nucleus and putamen e ile ea baloa ho sebelisoa coefflement ea (nonparametric) ea boemo ba Spearman. Maemong ohle, ho se tšoane ho ne ho nkuoa ho le bohlokoa ka lipalo ha p

Results

Ho nahana ka PET nakong ea ho itima lijo

DVR e tloaelehileng khubung ea caudate e ne e phahame haholo ho litšoene tse hlaheletseng ha li bapisoa le litšoene tse tlasa lefatše (t10= 2.96, p<0.05; Feie. 1). Litšoene tse mahareng le tsona li ne li e-na le DVR e phahameng ka ho fetisisa ho putamen, empa phapang ena ha ea ka ea fihlela bohlokoa ba lipalo (p= 0.121).

Feie. 1  

Phumano ea li-receptor tsa D2 ([18F] FCP DVR) khubung ea caudate le putamen ho tse hlano tse hlahelletseng (D) le ba tlase ba supileng (S) litšoene. Mangolo supa litšoene ka bomong (bona Lethathamo 1). Mohala o otlolohileng e bolelang moelelo [18F] FCP DVR. *p

Karabelo e bolokiloeng ke lijo nakong ea ho itšila

Palo ea (± SEM) ea lipalo tsa li-reinforcers le bolele (± SEM) litekanyetso (likarabo ka motsotsoana) ho feta likarolo tse hlano tsa ho qetela tsa boits'oaro pele ho manollo ea PET ea litšoene e bonts'oa ho Lethathamo 1. Ha ho na lintho tsena tse fapaneng tse fapaneng ka ho felletseng kamoo ho boletsoeng t liteko.

Karabo ea bongoaneng

Kruskal-Wallis ANOVA e bontšitse phello e kholo ea sehlopha ho latency ho ama ntho e ncha (K= 8.73, p<0.05). Joalokaha ho bontšitsoe ho Feie. 2Matsoalo a litšoene tse hlaheletseng tse amang ntho e ncha a ne a le telele haholo ho feta a ka tlase ho (Mann-Whitney) U= 3.00, p<0.05) le litšoene tse nang le bolulo ka bomong (Mann-Whitney U= 2.00, p<0.01). Lihlopha tsena tse peli tse qetellang li ne li sa fapana haholo. Ntle le moo, ho litšoene tse nang le boiphihlelo sechabeng, kamano e ntle e ile ea bonoa lipakeng tsa latency ho ama ntho e ncha le ho fumaneha ha receptor ea D2 mokokotlong oa caudate (Feie. 3; Spearman rho = 0.663, p<0.05) empa eseng ho putamen (Spearman rho = 0.4718, p= 0.122).

Feie. 2  

Boemo ka metsotsoana e seng mekae ho ama ntho e nooang ho tse hlano tse hlahelletseng (DOM), beng ka tlase ba supileng (Sub), le ba robong ka tlung e le 'ngoeLeslie) litšoene. Mangolo supa litšoene ka bomong (bona Lethathamo 1), *p
Feie. 3  

Kamano pakeng tsa phumaneho ea li-receptor tsa D2 ([18F] FCP DVR) ka har'a motsoako oa caudate kapa setamen le karabelo e ncha (litubu ka motsotsoana ho ama ntho e itseng) ho litšoene tse bolokiloeng sechabeng

Puisano

Patlisiso ea pejana ho litšoene e bonts'itse hore ho fihlela bosholu ba sechaba ho hokahana le keketseho ea ho fumaneha ha D2 sebakeng sa basal ganglia le kutloisiso e tlase ea litlamorao tsa cocaine ha li bapisoa le litšoene tse tlasa lefatše.Morgan et al. 2002). Lintlha li boetse li bontšitse kamano e fapaneng pakeng tsa ho fumaneha ha D2 receptor le kutloelo-pele ho litlamorao tse matlafatsang tsa koae, joalo ka ha ho bonoa lithutong tse ling ho liphoofolo tsa laboratori le batho (Volkow et al. 1999; Thanos et al. 2001; Nader et al. 2006; Dalley et al. 2007). Kamora hore litšoene li sebetse k'hok'heine ka lilemo tse 'maloa, ho fumaneha ha li-D2 sebakeng sa caudate le putamen ha li sa fapana lipakeng tsa litšoene tse hlaheletseng le tse tlasa maemo, leha ho ntse ho tsoela pele ka matlo a boiketlo ba sechaba (Czoty et al. 2004). Phuputsong e teng hona joale, liphapang tse amanang le boemo ba D2 li fumaneha hape ha litšoene li lula malapeng a bona nakong ea ho itšunya-tšunya ka har'a k'hok'heine. Kamora likhoeli tse ka bang 8 tsa ho khaotsa ho sebelisa koae, ho fumaneha ha D2 ka bongata khubung ea litšoene tse hlahelletseng e ne e le 26% e phahame ho feta ea batho ba ka tlasa lefatše. Phumano ea D2 ho putamen e ne e le 15% e phahameng ho litšoene tse ngata ha e bapisoa le ba maemong a tlase, empa ho fapana hoa batho ka bomong ho ne ho le ho lekane ho thibela bohlokoa ba lipalo. Lintlha tsena li fana ka bopaki ba neuroplasticity e le hore, ho sa natsoe lilemo tse ngata tsa ho pepeseha matsatsi a / cocaine ea boithatelo ea 5 matsatsi a / beke, li-receptor tsa D2 tsa boko li ile tsa lula li arabela maemong a tikoloho ha ho pepesetsoa koae. Ntle le moo, litšoene tse hlaheletseng li ne li sa sebetse hantle ho feta batho ba tlasa maemo a tlase, mme mohato ona o ne o kopantsoe hantle le ho fumaneha ha D2 receptor sebakeng sa caudate.

Boithuto ba rona ba mantlha bo bontšitse hore phumaneho ea li-receptor tsa D2 e eketsehile ho litšoene e ileng ea e-ba matla empa e ne e sa fetohe ho ba ka tlase ho (Morgan et al. 2002). Re nahanne ka maemo a phahameng a puso e le mohopolo o tsoelapele oa khatello ea kelello ho tloha ho khatello e sa ts'oaneng e fumanoeng ke litšoene tse tlase ho isa ho ruileng tikoloho e fumanoeng ke liphoofolo tse hlahelletseng (Nader le Czoty 2005). Ka hona, tlhaloso e 'ngoe ea sephetho sa hona joale ke hore phapang e amanang le boemo bo fumanehang ka har'a D2 receptor e bonoang kamora ho qeta likhoeli tsa 8 ke lebaka la ho pepesehela ho ruisa tikoloho ho litšoene tse hlaheletseng. Qalong ea liteko tsena, re ne re rerile ho hlahloba tšibollo ena ka ho khetha phetoho ea liperesente tsa litšoene ka bomong [18F] FCP DVRs pele ho moo (ke hore, Czoty et al. 2005b) le nakong ea bootsoa. Ka bomalimabe, papiso ena e ne e thatafalloa ke liphetoho lipakeng tsa maemo a bophelo tse etsahetseng nakong ea ha litšoene tse ling li thibetsoe. Ho ka etsahala hore sephetho sa hona joale se ka ameha ke ho se tšoane ha litekanyetso kapa boholo ba ho fola ho fokotseha ha phihlello ea D2 receptor e hlahisitsoeng ke ho ipusa nako e telele ea cocaine, ketsahalo eo re neng re e bonts'a pele litšoeneng tsa rhesus ka bomong.Nader et al. 2006). Ho bohlokoa ho tseba, leha ho le joalo, karolelano ea nako e fetileng ea cocaine ea litšoene ho Nader et al. (2006) thuto e ne e batla e phahame makhetlo a leshome ho feta ea litšoene thutong ea hona joale (787.8 ± 128.0 mg / kg dhidi ea 84.4 ± 29.7 mg / kg). Leha litaba tsena li thatafatsa kutloisiso ea lits'ebetso tseo litšoene tse busang le tse katlase li ileng tsa fapana ka ho fumaneha ha D2 receptor, kamora likhoeli tse ka bang 8 tsa ho ila, li-DVR tsa litšoene tse phahameng li ne li phahame haholo ho feta tsa batho ba tlasa lefatše. Bohlokoa ba bongaka ba ho fumana hona bo atamelaneng le ponahalong ea tšebetso ea methapo ea methapo ea DA e tataisoang ke tikoloho, e fana ka maikutlo a hore boko ba motho ea ts'ehetsang koae bo ka lula bo amohela liphetoho tse ntle tikolohong.

Morero o mong oa lithuto tsena e ne e le ho hlahloba kamano lipakeng tsa boiphihlelo ba sechaba, ho fumaneha ha li-D2, le karabelo ho bocha - tšobotsi e amanang le tlokotsi e atileng ea litlamorao tse matlafatsang tsa lithethefatsi tse hlekefelitsoeng (mohlala, Piazza et al. 1989, 2000; Bardo et al. 1996). Phuputsong ea hona joale, litekanyo tse tloaelehileng tsa litšoene tse hlahelletseng ho ama ntho e sa tsoa beoa terakeng ea lapeng e ne e le telele haholo ho feta ea litšoene tse tsamaisang thepa e ikemetseng ebile li le kahare ka boeona, li fana ka maikutlo a hore boiphihlelo ba ho ba matla (ke hore, moruo oa tikoloho) bo theotse tekanyo ena ea karabelo ho bohloka. Ho bohlokoa ho hlokomela hore lithuto tsa pejana li ile tsa hlahloba liphihlelo tsa pele tsa li-cocaine, athe litšoene lithutong tsa hona joale li ne li e-na le boikoetliso bo bongata ba ho ikoetlisa. Kahoo, moelelo o mong oa bohlokoa oa liphetho tsena ke hore tšusumetso ea puso ea sechaba ka sechaba mabapi le maikutlo a macha ha ea ka ea felisoa ka lebaka la nalane ea litšoene ea ho sebelisa koae. Tlhaloso e 'ngoe ke hore liphapang tse fapaneng e kanna ea ba tsa ba tsa pele matlo a bolulo mme tsa ba le tšusumetso ho thehoeng hoa maemo. Ka mantsoe a mang, ho ka etsahala hore litšoene tse tloahelang ho etsa bocha li bocha li be maemong a tlase. Ho ts'ehetsa monyetla ona, litšoene tsa litšoene tsa basali tsa cynomolgus ho ama ntho e sa tsoa hlahlojoa pele ho matlo a boiketlo ba batho e ne e le ponelopele ea maemo a sechaba a bophelo, mme tataiso ea litlamorao e ne e ts'oana le e boneng thutong ea hona joale (Riddick et al. 2009). Phuputsong ena, leha ho le joalo, bolelele ba litšoene tse tona tse nang le ntlo e le 'ngoe li ne li le tlase ka mokhoa o fokolang oa ho fana ka maikutlo a hore li ka bolela bokamoso ba boemo ba motho sechabeng. Ebile, ha litšoene tsena li ne li qetella li kentsoe lihlopheng tsa maemo a bophelo, boemo ba morao bo ne bo sa boletsoe esale pele ke ho ts'oara ntho e ncha (e sa bontšoang). Re lokela ho hlokomela, leha ho le joalo, hore thutong ea hona joale, papiso e totobetseng ea litšoene le ntle le boiphihlelo sechabeng e ka ferekanngoa ke boiphihlelo ba koae ka boomo. Lintlha tse hlahisang phapang lipakeng tsa sephetho sa litšoene tse tona le tse tšehali li sa ntse li lokela ho hlahlojoa empa e kanna ea ba ka lebaka la sampole e nyane thutong e teng hona joale.

Ha ho nahanoa hore litšoene tse hlahelletseng li na le ts'ebetso e phahameng haholo ea li-caudate nucleus D2 receptor fumaneha le litselana tse phahameng tsa ho ama ntho e ncha, ha ho makatse hore ebe mehato ena e 'meli ea morao e ne e amana hantle. Lintlha tsena li tsamaisana le data ea PET bathong e fanang ka maikutlo a kamano e fapaneng lipakeng tsa ho batla tse ncha le ho fumaneha ha D2Zald et al. 2008) le ho ts'ehetsa ho hokela khokahano lipakeng tsa D2 dopamine receptors le maemo a feto-fetohang a bonahatsoang litekong tsa laboratori tsa likarolo tse fapaneng tsa ho qobelloa ho kenyelletsa ho batla bocha. Radiotracer e sebelisitsoeng thutong ea hona joale, FCP, e tlama ho D2, D3, le D4 subtypes ea lelapa la D2 la li-receptors; lithuto tsa liphatsa tsa lefutso li thatafalitse li-subtypes tsena ho arabeleng karabelo ea bocha le mehato e meng e amanang le ho qobelloa (mohlala, Retz et al. 2003; Mufano et al. 2008). Ho feta moo, Dalley le basebetsi-mmoho (2007) ho tlalehiloe ka tlase ho fumaneha ha li-receptor tsa D2 ka har'a li-ligus tse fumanoeng li sa ts'oaroe haholo mme hamorao tsa ipehela palo e kholo ea koae. Leha lits'ebetso tsa kelello li lekantsoe ke liteko tse fapaneng tsa "laborator" le "ho qhoebeshana" le phapang pakeng tsa likarolo tsa mocheso joalo ka ha li lekiloe bathong le liphoofolong ha li hlake.Dellu et al. 1996; Stoffel le Cunningham 2007), bokhoni ba ho nahana esale pele ba mehato ena bo bonts'a hore li emetse mokhoa o ts'epahalang oa boits'oaro o bonts'ang kotsi e ntlafalitsoeng liphellong tse amanang le tlhekefetso tsa psychostimulants. Ho feta moo, lithuto tsa hona joale le tse fetileng ho litšoene tse bolokiloeng sechabeng (Morgan et al. 2002; Czoty et al. 2004, 2005b) bontša hore lintlha tsena tse tharo li ka susumetsoa ke mefuta ea tikoloho. Ka ho khetheha, ba tšehetsa mohopolo o tsotehang oa hore matla a sechaba ke mokhoa oa ho ruisa tikoloho o ka bakang keketseho ea phihlello ea D2 receptor, ea fokotseha ka karabelo ea bohloka (ke hore, lat latous ea ho atamela le ho ama ntho e itseng), mme e fokotseha ha kutloisiso ea ho litlamorao tse amanang le tlhekefetso ea koae. Ho ngaka, lithuto tsena li khothaletsa hore liphetoho tse ntle tikolohong ea motho ea sebelisang lithethefatsi hampe e ka ba karolo e sebetsang ea kalafo ea tlhekefetso ea lithethefatsi.

lumela hore baa fokola

Patlisiso ena e ne e tšehelitsoe ke National Institute on Drug Abuse Aid R37 DA10584. Bangoli ba tlaleha ho se lumellane ha lithahasello mme ba ka thabela ho amohela thuso ka tlhahlobo ea nchafatso ea ntho e entsoeng ke Drs. Allyson Bennett le Peter Pierre le thuso ea botekgeniki ea Kimberly Black, Robert W. Gould le Michelle Icenhower.

References

  1. Bardo MT, Donohew RL, Harrington NG. Psychobiology ea ho batla bocha le boitšoaro ba ho batla lithethefatsi. Behav Brain Res 1996; 77: 23-43. [E fetotsoe]
  2. Czoty PW, Morgan D, Shannon EE, Gage HD, Nader MA. Tšobotsi ea ts'ebetso ea dopamine D1 le D2 receptor ts'ebetsong ea litšoene tsa cynomolgus tse ikemetseng. Psychopharmacology. 2004; 174: 381-388. [E fetotsoe]
  3. Czoty PW, Gage HD, Nader MA. Ping ea PET ea li-receptor tsa driamine dopamine D2 li-primates tse se nang botho: keketseho ea ho fumaneha ho hlahisoang ke kalafo e sa foleng ea raclopride. Synfall. 2005a; 58: 215-219. [E fetotsoe]
  4. Czoty PW, McCabe C, Nader MA. Tlhahlobo ea matla a matlafatsang a koae ho litšoene tse bolokiloeng sechabeng ho sebelisa mokhoa oa khetho. J Theracol Exp Ther. 2005b; 312: 96-102. [E fetotsoe]
  5. Czoty PW, Gould RW, Nader MA. Kamano lipakeng tsa maemo a sechaba le cortisol le ho teba ha testosterone ho litšoene tsa banna ba cynomolgus (Macaca fascicularis) J Neuroendocrinol. 2009; 21: 68-76. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
  6. Dalley JW, Fryer TD, Brichard L, Robinsin ES, Theobald DE, Laane K, Pena Y, Murphy ER, Shah Y, Studst K, Abakumova I, Aigbirhio FI, Richards HK, Hong Y, Baron JC, Everitt BJ, Robbins TW . Li-receptor tsa nyutlelie D2 / 3 receptors li bolela tšusumetso ea ts'usumetso le matlafatso ea koae. Mahlale. 2007; 315: 1267-1270. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
  7. Dawe S, Loxton NJ. Karolo ea ho potlaka ho matlafatseng tlhekefetso ea lithethefatsi le mathata a ho ja. Neurosci Biobehav Rev. 2004; 28: 343-351. [E fetotsoe]
  8. DeGrado TR, Turkington TG, Williams JJ, Stearns CW, Hoffman JM, Coleman RE. Litšobotsi tsa ts'ebetso ea sekenara sa PET ea 'mele oohle. J Nucl Med. 1994; 35: 1398-1406. [E fetotsoe]
  9. Dellu F, Piazza PV, Mayo W, Le Moal M, Simon H. Novelty-ea batlang litšoene-litšobotsi tsa boits'oaro le kamano e ka bang teng le tšekamelo ea ho batla maikutlo ho motho. Neuropsychobiology. 1996; 34: 136-145. [E fetotsoe]
  10. Grant KA, Shively CA, Nader MA, Ehrenkaufer RL, Line SW, Morton TE, Gage HD, Mach RH. Matla a boemo ba sechaba sechabeng ho litšoaneleho tse amohelang li-dopamine D2 receptor e kopantseng litšoene tsa cynomolgus tse hlahlojoang ka positron emission tomography. Synfall. 1998; 29: 80-83. [E fetotsoe]
  11. Hooks MS, Jones GH, Smith AD, Neill DB, Justice JB., Jr Karabo ho bonoa bo boletsoeng esale pele bo bolela karabelo ea locomotor le nucleus accumbens ho koae. Synfall. 1991; 9: 121-128. [E fetotsoe]
  12. Kaplan JR, Manuck SB, Clarkson TB, Lusso FM, Taub DM. Boemo ba sechaba, tikoloho le atherosclerosis ho litšoene tsa cynomolgus. Arteriosulinosis. 1982; 2: 359-368. [E fetotsoe]
  13. Logan J, Fowler JS, Volkow ND, Wang GJ, Ding YS, Alexoff DL. Karolelano ea boholo ba phasalatso ntle le sampole ea mali ho tsoa tlhahlobisong ea setšoantšo sa PET. J Cereb flow flow Metab. 1996; 16: 834-840. [E fetotsoe]
  14. Mach RH, Moholo ST, Morton TE, Nowak PA, Evora PH ,criptko JG, Luedtke RR, CD ea Unsworth, Filtz T, Rao AV, et al. Ts'ebeliso ea [18F] 4-fluorobenzyl iodide (FBI) ho tlhahiso ea radiotracer ea PET: lithuto tsa alkylation ea mohlala le ts'ebeliso ea eona ho moralo oa li-dopamine D1 le D2 receptor-agents imaging. Nucl Med Biol. 1993a; 20: 777-794. [E fetotsoe]
  15. Mach RH, Luedtke RR, CD ea Unsworth, Boundy VA, Nowak PA, DRMko JG, Moholo ST, Jackson JR, Hoffman PL, Evora PH, et al. Li-benzamides tse 18F tse ngotsoeng bakeng sa ho ithuta dopamine D2 receptor e nang le positron emission tomography. J Med Chem. 1993b; 36: 3707-3720. [E fetotsoe]
  16. Mach RH, Nader MA, Ehrenkaufer RL, Line SW, Smith CR, Luedtke RR, MP MP, Kung HF, Lyons D, Morton TE. Ho bapisoa ha mefuta e 'meli ea fluorine-18 e bitsoang benzamide e tlamellang hape ho dopamine D2 receptors: lithutong tse tlamang tsa vitro le positron emission tomography. Synfall. 1996; 24: 322-333. [E fetotsoe]
  17. Mach RH, Nader MA, Ehrenkaufer RL, Line SW, Smith CR, Gage HD, Morton TE. Ts'ebeliso ea positron emission tomography ho ithuta ka matla a tlhahiso ea dopamine ea psychostimulant-ikiwa. Pharmacol Biochem Behav. 1997; 57: 477-486. [E fetotsoe]
  18. Morgan D, Grant KA, Prioleau OA, Nader SH, Kaplan JR, Nader MA. Bo-ralitaba ba boemo ba sechaba sechabeng sa litšoene tsa cynomolgus (Macaca fascicularis) kamora sehlopha. Ke J Primatol. 2000; 52: 115-131. [E fetotsoe]
  19. Morgan D, Grant KA, Gage HD, Mach RH, Kaplan JR, Prioleau O, Nader SH, Buchheimer N, Ehrenkaufer RL, Nader MA. Bolaoli ba sechaba ho litšoene: li-dopamine D2 receptors le ho itaola ka koae. Nat Neurosci. 2002; 5: 169-174. [E fetotsoe]
  20. Mufano MR, Yalcon B, Wills-Owen SA, Flint J. Association of the dopamine D4 receptor (DRD4) mofuta oa botho le litšoaneleho tse amanang le tsela e atamelaneng: tlhahlobo ea meta-data le data e ncha. Psychology ea Biol. 2008; 63: 197-206. [E fetotsoe]
  21. Nader MA, Czoty PW. Boithuto ba monahano ba PET ba li-receptor tsa dopamine D2 mefuteng ea litšoene tsa tlhekefetso ea cocaine: tsoelopele ea liphatsa tsa lefutso le phallo ea tikoloho. Ke J Psychiatry. 2005; 162: 1473-1482. [E fetotsoe]
  22. Nader MA, Grant KA, Gage HD, Ehrenkaufer RL, Kaplan JR, Mach RH. PET imaging ea dopamine D2 receptors e nang le [18F] fluoroclebopride ho litšoene: litlamorao tsa isoflurane- le ketamine-indied anesthesia. Neuropsychopharmacology. 1999; 21: 589-596. [E fetotsoe]
  23. Nader MA, Morgan D, Gage HD, Nader SH, Calhoun T, Buchheimer N, Ehrenkaufer R, Mach RH. PET ea ho nahana ka li-receptor tsa dopamine D2 nakong ea boits'oaro bo sa feleng ba koae ho litšoene. Neurosci ea tlhaho. 2006; 9: 1050-1056. [E fetotsoe]
  24. Perry JL, Larson EB, JP ea Jeremane, Madden GJ, Carroll ME. Impulsivity (theolelo ea ho liehisa) e le ponelopele ea ho fumana boits'ireletso ba IV cocaine liphatseng tsa basali. Psychopharmacology. 2005; 178: 193-201. [E fetotsoe]
  25. Piazza PV, Deminiere JM, Le Moal M, Simon H. Lintho tse hlalosang ts'oaetso ea motho ka mong ho amphetamine ea botho. Saense. 1989; 245: 1511-1513. [E fetotsoe]
  26. Piazza PF, Rouge-Pont F, Deminiere JM, Kharoubi M, Le Moal M, tšebetso ea Siman H. Dopamine e fokotsehile ka cortex ea pele mme e eketseha ka li-nucleus tsa rubus tse reriloeng pele ho nts'etsapele tsamaiso ea amphetamine. Brain Res. 1991; 567: 169-174. [E fetotsoe]
  27. Piazza PV, Deroche-Gamonet V, Rouge-Pont F, Le Moal M. Liphetoho tse feto-fetohang tsa litekanyetso tsa ho itlhokofatsa-ho etsa mesebetsi e boletsoeng esale pele li kotsing ea ho lemalla lithethefatsi. J Neurosci. 2000; 20: 4226-4232. [E fetotsoe]
  28. Retz W, Rosler M, Supprian T, Retz-Junginger P, Thome J. Dopamine D3 receptor gene polymorphism le boits'oaro bo mabifi: amanang le ho ts'oenyeha le psychopathology e amanang le ADHD. J Neural Transm. 2003; 110: 561-572. [E fetotsoe]
  29. Riddick NV, Czoty PW, Gage HD, Kaplan JR, Nader SH, Icenhower M, Pierre PJ, Bennett A, Garg PK, Nader MA. Litšobotsi tsa boitsoaro le bo-neurobiological tse susumetsang sebopeho sa maemo a phahameng sechabeng ho litšoene tsa cynomolgus tsa basali. Neuroscience. 2009; 158: 1257-1265. [Tlhahiso ea mahala ea PMC] [E fetotsoe]
  30. Rouge-Pont F, Piazza PV, Kharouby M, Le Moal M, Simon H. E phahameng le khatello e telele ea khatello ea maikutlo ho dopamine ho tse hlokoang ke liphoofotsoana tsa liphoofolo tse ikemiselitseng ho amphetamine boipuso. Tlhahlobo ea Microbalal Brain Res. 1993; 602: 169-174. [E fetotsoe]
  31. Stoffel EC, Cunningham KA. Kamano lipakeng tsa karabelo ea locomotor tikolohong e ncha le boits'oaro bo bobe lithutong. Lithethefatsi. 2007; 92: 69-78. [E fetotsoe]
  32. Thanos PK, Volkow ND, Freimuth P, Umrgaki H, Ikari H, Roth G, Ingram DK, Hitzemann R. Ho ts'oaroa ha dopamine D2 receptors ho fokotsa taolo ea joala. J Neurochem. 2001; 78: 1094-1103. [E fetotsoe]
  33. Verdejo-Garcia A, Lacer AJ, Clark L. Impulsivity e le lets'oao le kotsing ea ho lemalla ts'ebeliso e mpe ea lithethefatsi: Tlhahlobo ea liphumano e theha lipatlisiso tse nang le kotsi e ngata, ba bechang ka mathata le lithuto tsa mokhatlo oa liphatsa tsa lefutso. Neurosci Biobehav Rev. 2008; 32: 777-810. [E fetotsoe]
  34. Volkow ND, Wang GJ, Fowler JS, Logan J, Gatley SJ, Gifford A, Hitzemann R, Ding YS, Pappas N. Phatlalatso ea ho matlafatsa likarabo ho li-psychostimulants ho batho ka boko D2 dopamine receptors. Amer J Psychiatry. 1999; 156: 1440-1443. [E fetotsoe]
  35. Zald DH, Cowan RL, Riccardi P, Baldwin RM, Ansari MS, Li R, Shelby ES, Smith CE, McHugo M, Kessler RM. Ho fumaneha ha "midbrain dopamine receptor" ho amana haholo le litšobotsi tse sa tloaelehang tsa batho. J Neurosci. 2008; 28: 14372-14378. [Tlhahiso ea mahala ea PMC] [E fetotsoe]