Bothata ba ho fumanoa ha methapo ea li-dopamine D2 ho bolela esale pele likarabo tsa thalamic le lipakeng tsa mekhoa ea boipheliso bakeng sa bahlaseli ba cocaine lilemo tse tharo hamorao (2010)

Synfall. Sengoloa se ngotsoeng; e fumaneha ho PMC May 1, 2011.

E hatisitsoe ka mokhoa o qetelle o hlophisitsoeng e le:

PMCID: PMC2840182

NIHMSID: NIHMS143048

Moetso oa khatiso oa ho qetela oa mohatisi o fumaneha ho Synapse

Sheba lihlooho tse ling ho PMC hore Qotsa sehlooho se hatisitsoeng.

Eya ho:

inahaneloang

Maemo a tlase a dopamine (DA) phumano ea li-receptor tsa D2 setulong sa phomolo e se e tlalehiloe ho batho ba lemaletseng lithethefatsi 'me ba amana le tšebelisano ea "metabolism" ea "perralal" le "dorsal". Phokotso ea ho fumaneha ha li-receptor tsa DA D2 hammoho le metabolism e fokotsitsoeng ea "ventral frontal metabolism" ho nahanoa hore e fana ka maikutlo a tlase a tefo ea moputso o seng oa lithethefatsi, tšobotsi ea mantlha ea ts'ebeliso ea lithethefatsi. Ka hona re khothaletsa hore phapang ea ho fumaneha ha li-D2 ho DA D2 ho tla thusa ka likarabo tse matla tsa moputso oa chelete bathong ba lemaletseng. Ho fumaneha ha li-receptor DA DXNUMX ho lekantsoe le [11C] raclopride le positron emission tomography le karabelo ho moputso oa chelete e ile ea lekanngoa (karolelano ea lilemo tsa 3 hamorao) ka ts'ebetso ea ho nahana ka matla a matla a matla a matla ho batho ba supileng ba lemaletseng koae. Liphetho li bonts'a hore ho fumaneha ha li-receptor tse tlase tsa DA D2 ho dorsal striatum ho ne ho amana le karabelo e theohileng ea thalamic ho moputso oa chelete; ha ho fumaneha ho tlase ho "cyral striatum" ho ne ho amahanngoa le ho eketseha ha kalafo ea medial prefrontal (Brodmann Area 6 / 8 / 32) ho fumana moputso oa chelete. Liphetho tsena tsa pele, tse hlokang ho phetoa ka mehlala e meholo ea sampole le ho netefatsoa ka taolo e phetseng hantle, li fana ka maikutlo a hore phomolo ea ho fumana litšebeliso ea DA D2 e bolela phapang e teng lipotsong tse sebetsang ho morekisi ea sa sebeliseng lithethefatsi (chelete) ho cortex ea pele, e kenelletseng tlhaisong ea boits'oaro. 'me ka thalamus, e khahliloe ke likarabo tse lebelletsoeng le tebello, ho batho ba lemaletseng koae.

Keywords: fMRI, PET, dopamine dopamine D2 receptor fumaneha, thalamus, preortal ea cortex, lekhoba la koae, moputso oa chelete.

Selelekela

Ho fokotseha ha methapo ea dopamine (DA) ho fumaneha ha li-D2 ho ba sebelisang lithethefatsi ho ka bonts'a neuroadaptations ea bobeli ho susumetso ea supraphysiological dopaminergic ho tsoa ho ts'ebeliso e mpe ea lithethefatsi (Volkow et al., 2004). Re sebelisa tšebeliso ea matla a matla a matla a khoheli (fMRI), haufinyane tjena re tlaleha maikutlo a boiketlo ba pele ba cortical ho fumana moputso oa chelete ho batho ba lemaletseng koae.Goldstein et al., 2007a). Ha ho fanoa ka setsoalle sa bohlokoa pakeng tsa ho phomola metabolism ea glucose kahare le dorsal prefrontal cortex (PFC) le phumano ea mantlha ea DA D2 receptor ho ts'ebeliso ea lithethefatsi tsa lithethefatsi (cocaine, methamphetamine le joala).Volkow et al., 2001; Volkow et al., 1993b; Volkow et al., 2007b), re fetoletse liphetho tsena tsa fMRI ho bonts'a maikutlo a fokotsehileng a meputso ho litheko tse seng tsa lithethefatsi ka ho lemalla tseo ka karolo e ka bonts'ang liphetoho lipuisisong tsa DA le ho fumaneha ha DA D2Volkow et al., 2007a). Leha ho le joalo, kamano e tobileng lipakeng tsa phetoho e matla (ke hore, ho arabela phephetso) karabelo e amanang le moputso ea PFC (le libaka tse ling tse nang le potoloho ea cortical ea striato-thalamic-prefrontal pele e neng e kenelletse ts'ebelisong ea lithethefatsi) ka motheo oa ho fumaneha ha li-DA D2 ho fumaneha ho batho ba lemaletseng lithethefatsi ba tlameha ho bontšoa.

Thutong ea pele ea hona joale re hokahanya tekanyo ea oksijene ea mali e itšetlehileng ka (BOLD) fMRI ho arabela mosebetsing oa ts'usumetso ea chelete ka ho fumaneha ha DA D2 receptor [e fumanoeng motheong oa phomolo le [11C] raclopride le positron emission tomography (PET), moelelo oa lilemo tsa 3 pele ho thuto ea fMRI ho batho ba lemaletseng koae. Re lekile khopolo-taba ea hore karabelo ea moputso oa chelete ho PFC (le libaka tse ling tsa potoloho ea cortical ea striato-thalamic-prefrontal cortical) e amana haholo le ho fumaneha ha li-receptor tsa DA D2 ho batho ba lemaletseng koae.

mekhoa

barupeluoa ba

Tlhahisoleseling e ne e fumaneha bakeng sa lithuto tse lemalloang tsa koae ka makhetlo a supileng (ba batona ba 5 le basali ba 2, kaofela Maafrika-Amerika, bona Lethathamo 1 bakeng sa demographic) e neng e nkile karolo lithutong tse peli tse phatlalalitsoeng tsa neuroimaging tse neng li phatlalalitsoe pele (Goldstein et al., 2007a; Volkow et al., 2006a; Volkow et al., 2006b). Barupeluoa ba ile ba fumana litekanyetso tsa ho kenyeletsoa lithutong tsena ka bobeli, joalo ka ha li netefalitsoe ke liteko tsa mmele, tsa methapo le kelello. Ka bokhutšoanyane, lithuto li ne li se na li-neuropsychiatric (ntle le ts'ebeliso e mpe ea lithethefatsi kapa ts'ebeliso), lefu la pelo, kapa endocrinological, ho kenyelletsa le ho phethahatsa litekanyetso tsa DSM-IV tsa ts'ebeliso ea hona joale ea koae kapa tlhekefetso. Lithuto tsohle e ne e le basebelisi ba mafolofolo bonyane likhoeli tse fetileng tsa 6 (mahala-kapa bokhopo, bonyane "ligrama tse 'ne" ka beke; bona Lethathamo 1 bakeng sa tse ling tse sebelisang lithethefatsi). Tšebeliso ea hona joale ea matekoane, li-barbiturates, amphetamines, kapa opiates e ile ea haneloa le ho ntlafatsoa ke liteko tsa pele tsa moroto. Ho ile ha fumanoa tumello e ngotsoeng bakeng sa lithuto tsohle kamora hore litsamaiso li hlalosoe ka hloko le tumellanong le Boto ea Thupelo ea Setheo sa lehae.

Lethathamo 1 

Litlhaloso tsa mohlala, ho kenyelletsa palo ea baahi, nalane ea tšebeliso ea koae le lintho tse ling tse sebetsanang le tšusumetso (tšusumetso, nako ea ho arabela le ho nepahala) le ho lumellana ha tsona le dopamine (DA) D2 fumaneha ka li-receptor (Bmax / Kd) ho caudate, putamen le ventral ...

Lintlha tsa PET

Lits'oants'o tsa PET li entsoe ka sekhatiso sa CTI 931 (Motorola, Knoxville, TN). Lintho li ile tsa hlahlojoa kamora ho entoa ka ente ea [11C] raclopride, e amanang haufi le DA D2 / D3 receptor radioligand. Lintlha tsa lits'ebetso tsa ho beha maemo, ho khahlapetsa motho ka letsoho le ho li chorisa, le ho hlalosoa ha radiotracer li hlalositsoe pele (Volkow et al., 1993b). Ka bokhutšoanyane, likhakanyo tse matla tsa metsotso ea 60 li ile tsa qalisoa hang ka mor'a ho kenngoa kahare ha 4-10 mCi ea [11C] raclopride (ts'ebetso e ikhethileng> 0.25 Ci / μmol ka nako ea ente). Nakong ea thuto, lithuto li ne li butsoe mahlo ka har'a kh'amera ea PET, kamore e ne e bonesitsoe hanyane, mme lerata le ne le fokolitsoe. Libaka tsa phaello (ROI) ho [11Litšoantšo tsa C] raclopride li ile tsa fumanoa bakeng sa dorsal (caudate, putamen) le ventral striatum le bakeng sa cerebellum, e neng e sebelisetsoa ho laola lintho tse sa tlangoang ka kotloloho. Bakeng sa thuto e 'ngoe le e' ngoe, li-ROI tsena tse tharo tsa pele li ile tsa khethoa skrineng se karolelitsoeng (tšebetso ho tloha 10 ho isa ho metsotso ea 60) 'me ea beoa tekong e matla, joalo ka ha ho hlalositsoe pele (Volkow et al., 1993b). Mosebetsi-nako oa curves bakeng sa [11C] raclopride ka har'a striatum le cerebellum le nako ea ts'ebetso ea nako bakeng sa tracer e sa fetoheng ho plasma li ile tsa sebelisoa ho lekanya palo ea lipehelo ka ho sebelisa mokhoa oa ho hlaka oa graphical bakeng sa lits'ebetso tse feto-fetohang (Logan et al., 1990). Paramente Bmax / Kd, e fumanoeng e le karo-karolelano ea bophahamo ba pokello ho striatum ho eo ho cerebellum minus 1, e sebelisitsoe e le mohlala oa paramente ea DA D2 receptor. Lintlha tsena tsa PET li fumanoe moelelo oa lilemo tsa 3.3 ± 1.2 pele ho data ea fMRI.

fMRI activation Paradigm

Kamora boikoetliso, lithuto li entse mosebetsi o hlokometsoeng tlas'a maemo a ts'usumetso ea lichelete tse tharo tse patiloeng ($ 0.45, $ 0.01, kapa $ 0.00). Ka ho khetheha, lithuto li ile tsa arabela (tsa tobetsa konopo) kapa tsa hana ho araba nakong ea ts'usumetso ea sekhahla (sekwere se khubelu), ho ipapisitse le tšusumetso ea thuto e fetileng [e fetotsoe ho tsoa ho (Thut et al., 1997)]. Ho bile le liteko tsa 18, lipara tse robong tsa khatiso le khatiso ea khatello, bakeng sa e 'ngoe le e' ngoe ea maemo a lichelete e neng e pheta makhetlo a tšeletseng / li-block [bona lintlha ho (Goldstein et al., 2007a; Goldstein et al., 2007b; Goldstein et al., 2007c)]. Nako e nepahetseng le nako ea karabelo e ile ea bokelloa mesebetsing eohle (Lethathamo 1). Ho latela tšusumetso ea bophelo ba nnete, lithuto li amohetse $ 50 bakeng sa mosebetsi ona, ho latela bonnete ba ts'ebetso. Ena e ne e le chelete e ngata hobane e imenne habeli chelete eo ba neng ba e fumana nakong ea thuto e felletseng. Bafo ba ne ba tseba maemo a meputso mosebetsing oohle. Mosebetsi ona o ile oa hlahisoa ke likhaba tse tsamaeang le MRI. Kamora ho phethela mosebetsi, lithuto li ile tsa lekanya maemo a bona a ho khahla le ho nyakalla maemong a mararo a lichelete ba sebelisa likala tse peli tsa pono (boholo: 0 ho 7, e thabisang ebile e le lerootho ho ho thabisa) mme moelelo oa litekanyetso tsena tse peli o sebelisitsoe e le mokhoa o sa tobang ea sepheo sa boikarabello ba mosebetsi (Lethathamo 1).

Tlhatlhobo ea data ea fMRI le Tlhahlobo ea Litšoantšo

Ho hlahlojoa ha MRI ho entsoe ho 4-T scanner ea MRI ea 'mele kaofela (Varian, Palo Alto, CA / Motorola, Berlin). Likarabo tsa BOLD li ile tsa lekanngoa ka T2 *-boima bo le bong bo nkiloeng ka nako e le 'ngoe bohloeki bo kopanyang (TE = 20, TR = 3500 msec, xNUMX-mm slice thickness, 4-mm crlic, hangata maqhubu a li-coronal tsa 1, tšimo ea pono = 33 cm, boholo ba 20 × 64 matrix, 64 ° flip angle, 90-kHz bandwidth e nang le sampling ea ramp, lintlha tsa nako ea 200, le likhatiso tse 'ne tsa dummy). Padding e ne e sebelisetsoa ho fokotsa motsamao, o neng o le kahare ho kamohelo e amoheloang ea ho fallisoa ha 91-mm ka ho fetesisa (1% ea boholo ba voxel) le ho potoloha ha 32 °, joalo ka ha ho tlaleha hang kamora ho matha ka seng (Caparelli et al., 2003). T1 e boima ba likarolo tse tharo e lekantsoeng ea likarolo tse tharo tse lekantsoeng tse lekanang (Lee le al., 1995) e ne e sebelisetsoa ho nahana ka sebopeho; Litšoantšo tsohle tsa MRI li ile tsa hlahlojoa ho khaola tlhekefetso e kholo ea morphological.

Lihlahlobo tsohle tsa nako li fetotsoe ka sebopeho sa SPM99 (Lefapha la Chelete ea Cognitive Neurology, London). Ho ile ha sebelisoa phetoho e tsitsitseng ea paramente ea likarolo tse tšeletseng (li-rotations tse tharo, liphetolelo tse tharo) bakeng sa setšoantšo sa molumo ho lokisa ho sisinyeha ha hlooho. Lisebelisoa tse hlophisitsoeng tse hlophisitsoeng hape li ne li thathamisitsoe ho Talairach foreimi ka 12-paramente affine change (Ashburner et al., 1997) ka ho sebelisa boholo ba voxel ba 3 × 3 × 3 mm3. XernUMX ea limilimithara tse bolelele ba 8-mm e ne e sebelisetsoa ho theola data. Moetso oa kakaretsoFriston et al., 1995) le moralo oa likoloi tsa lebokose o kentsoeng ka mokhoa o hlakileng oa karohano ea karodynamic li ile tsa sebelisoa ho lekanya limmapa tsa ts'ebetso. Letoto la linako le ne le hlonngoe ka ts'ebetso ea karabo ea hemodynamic e le sefahla-tsela sa tlase le sekepe sa 1 / 750-sa bobeli se khaotsoeng joalo ka faele e fetisang. Bakeng sa thuto e 'ngoe le e' ngoe, lipapatso tse tharo li qapiloe (45 ¢, 1 ¢, kapa 0 ¢ vs baseline average in all the sita task run).

Lipatlisiso tsa Statistical

Lits'ebetso tse tharo tse thehiloeng ho voxel tse thehiloeng ho 'mele (bokong ka bophara) pakeng tsa likarabo tsa BOLD fMRI (chelete e' ngoe le e 'ngoe e fapaneng le karolelano ea fixation) le ho fumaneha ha DA D21 caudate, putamen le ventral striatum (ke hore, litekanyetso tsa Bmax / Kd ho e 'ngoe le e' ngoe ea li-ROI tsena tse tharo li sebelisitsoe e le litekanyetso tsa peo) li ile tsa etsoa (bakeng sa litlhahlobo tse robong). Liphuputsong tsohle tsa boko bo felletseng, lipalo-palo li behiloe ho p <.05 boemo ba sehlopa bo lokisitsoeng (bonyane Z = 2.5 kapa T = 4.03) ka bonyane ba li-voxels tse 5 tse khahlisang (135 mm3). Hobane re entse tlhahlobo ea litlolo tse robong, re boetse re sebelisitse tokiso ea Bonferroni ho itšireletsa khahlanong le phoso ea Mofuta oa I (ke hore, boemo ba bohlokoa ba lebitso bo behiloe ho p≤.006 e lokisitsoe).

Bakeng sa litlhaloso tse hlalosang, re boetse re tsamaisitse likhokahano lipakeng tsa lipalo tsa batho bohle le mesebetsi e amanang le mosebetsi ka ho fumaneha ha DA D2 receptor (Lethathamo 1) le ka BOLD fMRI ROI tse khethiloeng (mona ho sebelisitsoe sehlopha sa maxima voxel). Ho itšireletsa khahlanong le phoso ea Mofuta oa I, bohlokoa ba lebitso bo ile ba beoa maemong a bohlale ba lelapa la p <.01 bakeng sa likamano tsena tsa tlhahlobo.

Results

Litlabano tsa bohlokoa lipakeng tsa DA D2 receptor phumaneho le likarabo tsa FMRI BOLD ho moputso oa chelete (45 ¢) li ile tsa bonoa tsa ba tsa kenyelletsa PFC le thalamus e le sephetho sa mantlha (Lethathamo 2 'me Setšoantšo sa 1). Ka ho khetheha, likarabo tsa thalamic BOLD fMRI ho moputso o phahameng oa chelete (45 ¢) li amana hantle le ho fumaneha ha DA D2 receptor ka har'a caudate (Setšoantšo sa 1A) ka mokhoa o ts'oanang bakeng sa putamen (data e sa bontsitsoeng). Letshwao la BOLD fMRI ka hara gram ea supramarginal le bonts'itse khokahano e ts'oanang le ho fumaneha ha DA D2 receptor ho putamen. Ho feta moo, karabelo ea fMRI ho moputso ona o phahameng oa lichelete sebakeng se nepahetseng sa gorsus [Brodmann Area (BA) 6 / 8 / 32] amanang hantle le phumaneho ea li-receptor tsa DA D2 ho proral striatum (Setšoantšo sa 1B). Litokiso tsena (Setšoantšo sa 1) li ne li ntse li fumanoa kamora ho ts'oara (ka likamano tse sa arohaneng) ho lieha ha nako lipakeng tsa fMRI le PET le lilemo tsa ts'ebeliso ea cocaine (r> | .95 |, p <.01). Likamano tsena ha lia ka tsa bonoa bakeng sa moputso o tlase oa chelete (1 ¢) kapa nakong eo e seng moputso (0 ¢).

Setšoantšo sa 1 

Localization (ka ho le letšehali) le splitplot (ka ho le letona) ea likhakanyo pakeng tsa (A) caudate DA D2 receptor phumaneho (joalo ka boleng ba peo) le thalamic (cluster maxima ho x = 9, y = −11, z = 14) Karabelo ea BOLD fMRI le pakeng (B) ventral striatum DA D2 receptor ...
Lethathamo 2 

Litlhakiso tsa bohlokoa (+) le tse mpe (-) (Pearson coeffnty) lipakeng tsa dopamine (DA) D2 receptor available (Bmax / Kd) ho caudate, putamen and ventral striatum (joalo ka boleng ba peo) le karabelo ea FMRI BOLD ho moputso oa chelete (45 ¢, ...

Litlhahlobo tsa Correlation li boetse li bonts'a tloaelo ea ho ba le kamano e ntle lipakeng tsa ventral striatum DA D2 receptor fumaneha le nako ea karabelo nakong ea maemo ohle a mosebetsi (Lethathamo 1). Leha ho le joalo, likamano tsena ha lia ka tsa pholoha khalemelo e bohlale ea lelapa. Kamora nako, ho ne ho e-na le moetlo oa khokahano e mpe lipakeng tsa likarabo tsa BOLD ka lehlakoreng le letona le holimo le holimo la gyrus ROI ka nako ea karabelo nakong ea boemo bo phahameng ba moputso (45 ¢, R = -0.78; p <0.05). Mekhoa e ts'oanang ha ea ka ea bonoa bakeng sa mefuta efe kapa efe e meng ea Lethathamo 1 le PFC kapa thalamic ROI mohlaleng ona.

Puisano

Liphetho tsa hona joale li bonts'a, ka lekhetlo la pele, likamano tsa bohlokoa lipakeng tsa DA D2 receptor phumano ho dorsal le ventral striatum le likarabelo tsa fMRI BOLD ho fumana moputso oa chelete ho batho ba lemaletseng koae. Ka ho khetheha, khokahano e mpe e ile ea bonoa pakeng tsa dorsal Supreme medial frontal gyrus [BA 6 / 8 / 32, e tlatsana le sebaka sa rostral cingulate joalo ka ha ho hlalositsoe ke (Ridderinkhof et al., 2004)] le ho fumaneha ha li-receptor tsa DA D2 sebakeng sa ventral striatum, hoo ho ka fokotsang ho fumaneha ha li-ventral striatal DA D2 receptor, ho phahama ha karabelo ea sebaka sena sa PFC ho moputso oa chelete. Ho fanoa ka hore batho ba lemaletseng koae ba bonts'a ho fumaneha ha DCNUMX ea DA e theotsoe (Volkow et al., 2004), e fokotsehileng metheo ea mantlha ea mantlha (Volkow et al., 1993b) le phokotso ea kutlo ea PFC ho moputso oa chelete (Goldstein et al., 2007a), tataiso ea khokahano ena e ne e sa lebelloa. Leha ho le joalo, lithuto tsa pejana li tlalehiloe ka mokhoa o tšoanang a mpe khokahano lipakeng tsa DA D2 receptor fumaneha ka har'a ventral striatum (moo khubung ea li-nucleus e fumanehang teng) le karabelo ea FMRI BOLD ho litekanyetso tse amanang le joala sebakeng se eketsehileng sa PFC (e kenyeletsang PFC ea moriana le rostral anterior cingrate cortex) lithutong tsa joala empa eseng ho mekhoa e metle ea taolo (Heinz et al., 2004). Liphetho tsa rona li holisa khokahano ena e mpe ho ea bobeli e seng lithethefatsi matlafatso. Ho ka etsahala hore batho ba lemaletseng koae ba nang le cocaine ba nang le phepelo e tlase ea "" D2 "receptor" le bona ke bona ba etsang hore sebaka sena sa PFC se hlohlellehe boits'oarong ba ts'ebetso ho fana ka maikutlo (Ridderinkhof et al., 2004), mohlomong ho lefella kutloisiso ea bona e fokolisitsoeng ea matlafatso ea chelete kapa bakeng sa ho eketseha ha bona ka matla. Ho ts'ehetsa phetolelo ena ke litumellano le nako ea karabelo nakong ea mosebetsi: ts'ebetso e potlakileng e ne e hokahanngoa le karabelo e kholo ea PFC ea moputso oa chelete le ho fumaneha ho tlase ha DA D2 ventral striatal receptor. Hlokomela hore leha thutong ea rona lintho tsena li sa fihle boemong ba bohlokoa ba bohlokoa, lithuto tse ling li sa tsoa hokahanya tlhahiso ea dopamine (Landau et al., 2009) le bokhoni ba ho kopitsa (dopamine)Cervenka et al., 2008) ka ts'ebetso ea kelello ho kenyelletsa linako tsa karabelo. Hape hoa etsahala hore lithuto tse lemalloang ke koae li nang le phihlello e tlase ea DA D2 receptor, eo le eena a ka bang le metabolism ea glucose e tlase ho basement (Volkow et al., 1993b), hlahisa phetoho e kholo ea matla ha e qholotsoa ho feta e nang le tšebetso ea li-receptor tse phahameng tsa DA D2 le metabolism e phahameng ea mantlha ea mantlha.

Ho fapana le hoo, ho ne ho bonoa melaetsa e nepahetseng bakeng sa thalamus e le hore e fumanehe ka hore DDNNXX e fumaneha ka har'a Dorsal striatum (e bohlokoa molemong oa caudate le mokhoa o ts'oanang bakeng sa putamen). The thalamus, sepheo sa mantlha bakeng sa DA's brain (Sanchez-Gonzalez et al., 2005), e na le karolo e kholo ho ntlafatseng boemo le tebello ea moputso. Mohlala, pejana re hlokometse likarabo tse kholo tsa thalamic metabolic ha methylphenidate, setlhare se matlafatsang se tšoanang le sa cocaine se thibela batsamaisi ba DA, se neng se lebelletsoe ho bapisoa le ha se ne se sa lebelloa (Volkow et al., 2003). Ka mokhoa o tšoanang, liteko tsa liphoofolo li bontša metabolism e kholo ea thalamic ha motsoako oa koae o sebelisoa sebakeng se nang le lithethefatsi ho feta nakong eo e sebelisoang likhoebong tsa lehae ho "likhotlo" tsa "addict" (Knapp et al., 2002) kapa ha re bapisa taolo ea koae e se nang khang e teng lipapatsong tse sa amaneng le batho (Porrino et al., 2002). Ntle le moo, re bonts'itse hape hore ho batho ba hlekefetsang koae, empa eseng maemong a taolo, methylphenidate e kenelletseng haholo e eketsehile DA ho thalamus mme keketseho ena e ne e lekana le botebo ba takatso ea litakatso tsa methylphenidate (Volkow et al., 1997). Ka hona, khokahano e tlalehiloeng hajoale e fana ka maikutlo a ho nka karolo ha dopaminergically modised ho kenella tebelong ea moputso oa chelete ho batho ba lemaletseng koae.

Ho hlakile hore liphetho tsa hona joale li hloka ho phetoa ka mefuta e meholo ea mehlala ea ba lemaletseng le ba laolehileng ba phetseng hantle. Ka ho khetheha, ho kenyelletsoa ha sehlopha sa taolo ho ne ho tla lumella ho hokahanya liphetho tsena ka kotloloho ho kamano e akaretsang lipakeng tsa DA D2 / D3 receptor phumaneho le tokiso ea moputso [hlokomela hore boithuto ba morao-rao bo bonts'itse kamano e ntle pakeng tsa ts'ebetso ea neural ea dopaminergic midbrain nakong ea tebello ea moputso (joalo ka ha ho lekantsoe) ka fMRI) le phihlello e amanang le moputso ea DA D2 e amanang le moputso mohahong oa ventral striatum ho baithaopi ba phetseng hantle ba 10 (Hakyemez et al., 2008)], kapa totobatsa hore na liphumano tsena li ikhethile ho ho lemalla koae. Tekanyetso e 'ngoe ea tlaleho ena ke nako e seng e fetile pakeng tsa lithuto tsa PET le fMRI, tseo ka nako ea 3 li neng li le kaholimo. Leha botsitso ba mehato ea PET bo phahame haholo [lithuto tsa liteko tsa morao-rao (le ho latela likhoeli tsa 19) li tlaleha ho fapana ho tlase ha [11C] raclopride binding e ka bang teng (phapang ea 7.9%) kapa bophahamo ba phano ea phetoho (phetoho ea 6-8%) le litheko tse phahameng tsa "intraclass" (0.81 - 0.90) tsamaisong ea dopaminergic e pakeng tsa methati e 'meli e arohaneng (Hietala et al., 1999; Schlösser et al., 1998; Uchida et al., 2009; Volkow et al., 1993a)], mehato ea ho lekola liteko ha e e-so etsoa ho batho ba hlekefetsang koae 'me ho ka etsahala hore e fetohe e le mosebetsi oa nalane ea lithethefatsi. Kahoo, liphetho tsa hajoale li hloka ho phetoa ho etsa litekanyo tsa PET le FMRI ka nako e le 'ngoe.

Ho akaretsa, ho emela phetisetso lithutong tse kholo ho batho ba lemaletseng ha ho bapisoa le taolo e phetseng hantle e tsamaeang le PET-fMRI ka nako e ts'oanang, liphetho tsa rona li bonts'a hore karabelo tsa PFC le thalamic ho moputso oa chelete bathong ba lemaletseng koae li ka fetoloa ka ho fumaneha ha DA D2 receptor ka hare-hare le dorsal striatum, ka ho latellana. Bohlokoa ba sephetho le boitšoaro bo ikhethileng, haholo bakeng sa lithethefatsi tse ling tse khothalletsoang ke lithethefatsi le lithethefatsi tse amanang le lithethefatsi [mohlala, (Martinez et al., 2007)], e hloka ho hlahlojoa lithutong tsa kamoso.

lumela hore baa fokola

Boithuto bona bo tšehelitsoe ke lithuso ho tsoa Setsing sa Naha sa Tlhekefetso ea Lithethefatsi (ho ea ho RZG: 1R01DA023579 le R21DA02062) le karolo e tsoang Ministerio de Ciencia e Innovación, Spain (SAF2007-66801); Lipatlisiso le Nchafatso ea Laboraro e tsoang Lefapheng la Matla la Amerika (OBER); le Setsi sa Patlisiso ea Kliniki e akaretsang (5-MO1-RR-10710).

Mongolo o botlaaseng ba leqephe

1Ho ne ho se na phapang e kholo ho fumaneha ha receptor ea DA D2 lipakeng tsa li-hemispheres ka bobeli (paired t <0.1, p> 0.9); litekanyetso li ile tsa lekanyetsoa bakeng sa litlhahlobo tsohle.

Tlhokomeliso: Buka ena e ngotsoe ke Brookhaven Science Associates, LLC tlasa Konteraka No. DE-AC02-98CHI-886 le Lefapha la Energy. Mmuso oa United States oa boloka, mme mohatisi, ka ho amohela sengoloa hore se phatlalatsoe, a amohela, lengolo la lefats'e ka bophara la ho phatlalatsa kapa ho hlahisa mofuta o phatlalalitsoeng oa buka ena e ngotsoeng ka letsoho, kapa ho lumella ba bang ho etsa joalo, molemong oa 'Muso oa United States.

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