I-acrylic: Lokhu kucwaninga ngokukhuluphala, kugxile kuma-recopors e-dopamine (D2) kanye nobudlelwano babo ekusebenzeni kwe-lobe esebenza phambili. Lolu cwaningo, olwenziwa yinhloko ye-NIDA, lukhombisa ukuthi ubuchopho bokudla ngokweqile kufana nalezo eziluthwa nezidakamizwa kulezi zinqubo ezimbili ezihloliwe. Njengomlutha wezidakamizwa, ama-onese anama-receptors we-D2 aphansi, kanye ne-hypofrontality. Ama-receptors we-D2 aphansi uyinto enkulu yokuphelelwa amandla (ukuphendula injabulo yenani) yesifunda somvuzo. I-Hypofrontality isho imetabolism ephansi ku-cortex yangaphambili, ehlotshaniswa nokulawulwa okungathandeki kokuziphatha, ukwanda kwesimo somoya, kanye nokwahlulela okungalungile kwemiphumela. Kubonakala sengathi kukhona ubudlelwano phakathi kwama-D2 receptors aphansi nokusebenza okuphansi kwama-lobes angaphambili. Okusho ukuthi, ukugcwala ngokweqile kuholela ekunciphiseni kwama-D2 receptors anomthelela kuma-lobes angaphambili./em>
I-Neuroimage. I-2008 Okthoba 1; I-42 (4): 1537-1543.
Ishicilelwe online 2008 Juni 13. doi: 10.1016 / j.neuroimage.2008.06.002.
UNora D. Volkow, ab * Gene-Jack Wang, c Frank Telang, b Joanna S. Fowler, c Panayotis K. Thanos, Jean Logan, c David Alexoff, c Yu-Shin Ding, d Christopher Wong, c Yeming Ma, b noKith Pradhanc
Isikhungo Sikazwelonke Sokuxhashazwa Kwezidakamizwa, eBethesda MD 20892, e-USA
b Isikhungo Sikazwelonke Ekusetshenzisweni Kotshwala Notshwala, iBethesda MD 20892, e-USA
c UMnyango Wezokwelapha Brookhaven National Laborator, Upton NY 11973, USA
d UMnyango We-Diagnostic Radiology, Yale University School of Medicine New Haven, CT 06520-8042, USA
* Umbhali ohambelana. I-National Institute on Drug Abuse, i-6001 Executive Boulevard, Igumbi 5274, eBethesda, MD 20892, e-USA. Ifeksi: + 1 301 443 9127. Amakheli e-imeyili: I-imeyili: [i-imeyili ivikelwe] , I-imeyili: [i-imeyili ivikelwe] (ND Volkow).
abstract
Indima kaDopamine kulawulo lokuvimbela yaziwa kahle futhi ukuphazanyiswa kwayo kungaba nomthelela ekuphazamisekeni kokuziphatha kokungalawuleki njengokukhuluphala. Kodwa-ke, indlela okungasebenzi kahle ngayo i-dopamine neurotransmission ephazamisa ukulawulwa kokuvimbela ayiqondakali kahle. Phambilini besikubhalile ukwehliswa kwama-dopamine D2 receptors ezifundweni ezikhuluphele ngokweqile. Ukuhlola ukuthi ukwehliswa kwe-dopamine D2 receptors kuhlotshaniswa nomsebenzi ezifundeni zobuchopho zangaphambi kokuthinteka ekulawuleni okungavimbeleki sahlola ubudlelwano phakathi kokutholakala kwe-dopamine D2 receptor ku-striatum ene-glucose glucose metabolism (umaka wokusebenza kobuchopho) ezifundweni eziyishumi ezikhuluphele ngokweqile (BMI> 40 kg / m2) bese uyiqhathanisa naleyo ekulawuleni okungakhuluphele okuyishumi nambili. I-PET yasetshenziswa ne- [11C] raclopride ukuhlola ama-receptors e-D2 kanye ne- [18F] FDG ukuhlola ubuchopho besifunda se-glucose metabolism. Ezifundweni ezikhuluphele ukutholakala kokutholwa kwe-D2 receptor kwakungaphansi kwezilawuli futhi kwahlanganiswa kahle ne-metabolism ku-dorsolateral prefrontal, medial orbitofrontal, anterior cingulate gyrus kanye ne-somatosensory cortices. Ekulawuleni ukuhlangana ne-prefrontal metabolism bekungabalulekanga kepha ukuqhathanisa nalabo abasezifundweni ezikhuluphele kakhulu bekungabalulekanga, okungavumeli ukuthi izinhlangano zihluke njengokukhuluphala kuphela. Izinhlangano ezihlangana phakathi kwe-striatal D2 receptors kanye ne-prefrontal metabolism ezifundweni ezikhuluphele ziphakamisa ukuthi ukwehla kwe-striatal D2 receptors kungaba nomthelela ekudleni ngokweqile ngokusebenzisa ukuguquguquka kwabo kwemigwaqo yangaphambi kokubeletha, ebamba iqhaza ekulawuleni okungavimbeli nokunikezwa kwesibindi. Ukuhlangana phakathi kwe-striatal D2 receptors kanye ne-metabolism kuma-somatosensory cortices (izifunda ezicubungula ukuzwela) kungahle kube enye yezindlela lapho i-dopamine ilawula khona ukuqiniswa kokudla.
Amagama agqamile: I-Orbitof Pambal cortex, i-Cingrate gyrus, eyokuqala ye-Dorsolateral, i-Dopamine ukuthutha, i-Raclopride, i-PET
Ukwanda kwesifo sokukhuluphala nezifo ze-metabolic ezihambisana nokubonile kule minyaka eyishumi edlule kuye kwaveza ukukhathazeka kokuthi uma kungalawulwa lokhu kungaba yingozi enkulu yezempilo yomphakathi evikelekile ngekhulu le-21st (Sturm, 2002). Yize izici eziningi zinomthelela kulokhu kukhuphuka kokukhuluphala ukwanda kokuhlukahluka kanye nokufinyelela kokudla okuthandekayo akunakubekelwa phansi (Wardle, 2007). Njengoba ukutholakala kokudla nezinhlobonhlobo kukhulisa amathuba okudla ngokweqile (ukubuyekeza Wardle, 2007) ukufinyelela okulula kokudla okukhangayo kudinga isidingo esivamile sokuvimbela isifiso sokukudla (i-Berthoud, 2007). Izinga abantu abahluka ngalo emandleni abo okuvimbela lezi zimpendulo futhi balawule ukuthi badla malini kungenzeka ukuthi balingise engcupheni yokudla ngokweqile ezindaweni zethu ezicebile zokudla (i-Berthoud, i-2007).
Sasikhombisile ukuthi kubantu abanempilo be-D2 ukutholakala kwe-receptor emaphethini wokuziphatha wokudla we-striatum (Volkow et al., 2003). Ngokuqondile ukuthambekela kokudla lapho kuvezwa imizwa engemihle kuhlangene ngokungafanele nokutholakala kwe-D2 receptor (the engezansi kwe-D2 receptors kuphakama amathuba umuntu angawadla uma ecindezelwe ngokomzwelo). Ngaphezu kwalokho, ocwaningweni oluhlukile, sikhombisile ukuthi izifundo zokuziphatha ngokweqile kwe-morbidly feta (BMI> 40) zaziphansi kunokujwayelekile ukutholakala kwe-D2 receptor ukutholakala futhi lokhu kuncishiswa kwakulingana ne-BMI yazo (i-Wang et al., 2001). Lokhu okutholwe kusiholele ekuthini sibeke eceleni ukuthi ukutholakala kwe-D2 receptor ephansi kungabeka umuntu engcupheni yokudla ngokweqile. Eqinisweni lokhu kuhambisana nokutholakele okukhombisa ukuthi ukuvimba ama-D2 receptors (imishanguzo ye-antipsychotic) kukhulisa ukudla futhi kuveza nengozi yokukhuluphala (Allison et al., 1999). Kodwa-ke izindlela ezisetshenziselwa ukutholakala kalula kwe-D2 receptor zandisa ingozi yokudla kakhulu aziqondakali.
Muva nje kukhonjisiwe ukuthi kuzilawuli ezinempilo ama-polymorphisms kuhlobo lwe-D2 receptor ahlotshaniswa nezinyathelo zokuziphatha zokulawulwa kokuvimbela (UKlein et al., 2007). Ngokuqondile, abantu abanokuhlukahluka kofuzo okuhambisana nesisho esiphansi se-D2 babenolawulo oluncane lokuvimbela kunabantu abanokuhlukahluka kofuzo okuhambisana nokuvezwa okuphezulu kwe-D2 futhi lezi zimpendulo zokuziphatha bezihlotshaniswa nokwehluka ekusebenzeni kwe-cingate gyrus (CG) kanye ne-dorsolateral prefrontal i-cortex (i-DLPFC), okuyizifunda zobuchopho ezibandakanyekile ezingxenyeni ezahlukahlukene zokulawulwa kokuvimbela (I-Dalley et al., 2004). Lokhu kusiholele ekucabangeni ukuthi kungenzeka ukuthi ubungozi obukhulu bokudla ngokweqile ezifundweni ezinokutholakala okuphansi kwe-D2 receptor nakho kungaqhutshwa ngumthetho we-DA we-DLPFC kanye nezifunda zangaphambi kwezempi, okukhonjiswe ukuthi zibambe iqhaza ekuvimbeleni ukuthambekela okungalungile kokuziphatha (Mesulam , 1985; Le Doux, 1987; Goldstein noVolkow, 2002). Ngakho-ke senze ukuhlaziywa kwesibili kwedatha evela ezifundweni ezazibuthwe phambilini njengengxenye yezifundo zokuhlola ushintsho kuma-D2 receptors (Wang et al., 2001) kanye ne-glucose glucose metabolism in obesity (Wang et al., 2002) nedatha evela Izilawuli ezifanayo. I-hypothesis yethu yokusebenza yayiwukuthi ukutholakala kwe-D2 receptor ezifundweni ezikhuluphele kakhulu kuzohlotshaniswa nomsebenzi ophazamisekile ezifundeni zangaphambili.
Kulolu cwaningo izihloko zokuziphatha ezikhuluphele ngokweqile nezifundo ezingezona ezikhuluphele zihlolwe ngePositron Emission Tomography (PET) ngokubambisana ne- [11C] raclopride ukukala i-DA D2 receptors (Volkow et al., 1993a) kanye ne- [18F] FDG ukukala ubuchopho i-glucose metabolism (Wang et al., 1992). Sifakazele ukuthi ama-receptors e-D2 e-DA azohlotshaniswa ne-metabolism ezindaweni ezisekuqaleni (i-DLPFC, CG kanye ne-orbitofrontal cortex).
Indlela
Tifundvo letifundvwa
Izifundo eziyishumi ezikhuluphele ngokweqile (abesifazane aba-5 nabesilisa aba-5, kusho ukuthi baneminyaka engama-35.9 ± 10 ubudala abanesisindo somzimba (BMI: isisindo ngamakhilogremu ahlukaniswe yisikwele sokuphakama ngamamitha) esingu-51 ± 5 kg / m2 kukhethwe echibini yezifundo ezikhuluphele eziphendule isikhangiso. Izifundo eziyishumi nambili ezingakhuluphele (abesifazane abayi-6 nabesilisa abayi-6, okusho ukuthi baneminyaka engama-33.2 ± 8 ubudala) abane-BMI esho engama-25 ± 3 kg / m2 abakhethiwe ukuqhathanisa. Ababambiqhaza bahlolwe ngokucophelela ngomlando wezokwelapha oningiliziwe, ukuhlolwa ngokomzimba nangokwemizwa, i-EKG, ukuhlolwa kwegazi okujwayelekile, kanye nobuthi bomchamo bezidakamizwa ze-psychotropic ukuqinisekisa ukuthi bayazifeza izindlela zokufakwa nezokukhishwa. Izindlela zokufaka yilezi: 1) amandla okuqonda nokunikeza imvume enolwazi; 2) BMI> 40 kg / m2 yezifundo ezikhuluphele kanye ne-BMI <30 kg / m2 yezihloko zokuqhathanisa kanye no-3) oneminyaka engama-20-55 ubudala. Izindlela zokukhishwa yilezi: (1) isifo samanje noma esidlule sezifo zengqondo kanye / noma sezinzwa, (2) ukuhlukumezeka kwekhanda ngokulahlekelwa ukwazi okungaphezu kwemizuzu engama-30, (3) umfutho wegazi ophakeme, isifo sikashukela nezimo zezokwelapha ezingashintsha ukusebenza kwe-cerebral, (4) ukusetshenziswa yemithi ye-anorexic noma izinqubo zokuhlinza zokwehlisa isisindo ezinyangeni eziyisi-6 ezedlule, (5) imishanguzo kadokotela emigqeni emasontweni ama-4 edlule, (6) umlando owedlule noma wamanje wokusebenzisa kabi utshwala noma izidakamizwa (kufaka phakathi ukubhema ugwayi). Izihloko ziyalelwe ukuthi ziyeke noma yimiphi imishanguzo yokuthenga noma izengezo zokudla okunempilo ngesonto eli-1 ngaphambi kokuskena. Ukuhlolwa komchamo kwangaphambi kokuskena kwenziwa ukuqinisekisa ukungabikho kokusetshenziswa kwezidakamizwa ngengqondo. Imvume esayiniwe enolwazi itholakele ezihlokweni ngaphambi kokubamba iqhaza njengoba kuvunyelwe iBhodi Yezokubuyekeza Yezikhungo e-Brookhaven National Laboratory.PET imaging
Isikali se-PET senziwa nge-CTI-931 (Computer Technologies, Incorporate, Knoxville, Tenn.) Tomograph (resolution 6 × 6 × 6.5 mm FWHM, 15 slices) nge [11C] raclopride and [18F] FDG. Imininingwane yezinqubo zokumiswa kwezikhundla, ezokwelashwa kanye nezokubopha izinzwa, ukushicilelwa kwama-radiotracer kanye nokudlulisela nokuskhipha okushicilelwe ku-[11C] raclopride (Volkow et al., 1993a), kanye ne- [18F] FDG (Wang et al., 1992) . Kafushane kwe- [11C] raclopride, ukuskena okunamandla kwaqalwa ngokushesha ngemuva kokulimala kwe-iv ye-4-10 mCi (umsebenzi othize> 0.25 Ci / μmol ngesikhathi sokujova) ingqikithi ye-60 min. Kwi- [18F] FDG, kuthathwe isikena esisodwa sokukhipha (i-20 iminithi) ngemuva komjovo we-iv we-35-4 mCi we- [6F] FDG. Ukusikwa kwenziwa ngosuku olufanayo; i- [18C] scanlopride scan yenziwe kuqala futhi yalandelwa yi- [11F] FDG, eyayilimale i-18 h ngemuva kwe- [2C] raclopride ukuvumela ukubola kwe-11C (i-half-life 11 min). Ngesikhathi izifundo bezigcinwa zilele kukhamera yePET amehlo abo evulekile; Igumbi lalikhanyelwe kancane nomsindo wawugcinwe okungenani. Umhlengikazi wasala nezifundo kuyo yonke inqubo ukuze aqinisekise ukuthi isifundo asilalanga phakathi nesifundo.
Ukuhlaziywa kwesithombe nedatha
Izindawo ezithintekayo (ROI) ezithombeni ze- [11C] raclopride zitholakele nge-striatum (caudate ne-putamen) kanye ne-cerebellum. I-ROI ekuqaleni yayikhethwe kwi-scan averved (umsebenzi ovela ku-10-60 min ye- [11C] raclopride), bese ibhekelwa kwizikali ezinamandla njengoba kuchaziwe ngaphambili (Volkow et al., 1993a). Umsebenzi wesikhathi wejika we- [11C] raclopride in striatum, kanye ne-cerebellum kanye nesikhathi ijika lesikhathi esingashintshiwe ku-plasma asetshenziselwa ukubala amanani asatshalaliswa (i-DV) kusetshenziswa inqubo yokuhlaziya engokomfanekiso yesistimu eguqukayo (Logan Plots) (Logan et al ., 1990). Ipharamitha i-Bmax / Kd, etholwe njengesilinganiso se-DV ku-striatum kuya ku-cerebellum (DVstriatum / DVcerebellum) minus 1, isetshenziswe njengepharamitha eyisibonelo yokutholakala kwe-DA D2 receptor. Le pharamitha ayizwakali ezishintshashintsheni ngokugeleza kwegazi lokugunda (uLogan et al., 1994).
Ukuhlola ukuhlobana phakathi kokutholakala kwe-D2 receptor kanye ne-brain glucose metabolism sihlanganise ukuhlobana sisebenzisa i-Statistical Parametric Mapping (SPM) (Friston et al., 1995). Imiphumela ye-SPM yabe isiqinisekiswa nezifunda ezithakaselwayo ezidonswe ngokuzimela (ROI); okungukuthi, izifunda ezitholwe kusetshenziswa isifanekiso esingaqondiswanga izixhumanisi ezitholwe ku-SPM. Ukuze kuhlaziywe i-SPM izithombe zezinyathelo ze-metabolic zenziwe zajwayelekile ngokwendawo kusetshenziswa isifanekiso esinikezwe kuphakheji ye-SPM 99 futhi kamuva sashelelwa nge-16 mm isotropic Gaussian kernel. Ukubaluleka kokuhlobanisa kwakusethwe ku-P<0.005 (engalungisiwe, ama-voxel angu-100) futhi amamephu ezibalo ambozwa esithombeni sesakhiwo se-MRI.Ngokuhlaziywa kwe-ROI sikhiphe izifunda sisebenzisa isifanekiso, esasishicilele ngaphambilini (Wang et al., 1992). Kulesi sifanekiso sikhethe ama-ROI e-medial and lateral orbitofrontal cortex (OFC), i-anterior cingulate gyrus (CG) kanye ne-dorsolateral prefrontal cortex (DLPFC) lapho sicabange ukuthi "i-priori" inhlangano nama-receptors e-DA D2, i-ROIs ye-caudate. kanye nama-putamen, okwakungama-ROI ayengama-striatal D2 receptors akalwa, futhi ama-ROI ku-parietal (i-somatosensory cortex ne-angular gyrus), yesikhashana (i-gyri yesikhashana ephakeme nephansi ne-hippocampus), nama-occipital cortices, i-thalamus ne-cerebellum, eyakhethwa njenge I-neutral ROIs.Ukuhlaziywa komzuzu womkhiqizo wePearson kwenziwa phakathi kokutholakala kwe-D2 receptor ku-striatum kanye nezinyathelo zesifunda ze-metabolic. Izinga lokubaluleka lokuhlobana phakathi kwama-D2 receptors kanye ne-metabolism yesifunda evela ku-ROI labekwa ku-P<0.01 futhi amanani we-P<0.05 abikwa njengamathrendi. Umehluko ekusebenzelaneni phakathi kwamaqembu uhlolwe kusetshenziswa ukuhlolwa okuphelele kokuqondana kokuhlehla nokubaluleka kwabekwa ku-P<0.05.
Imiphumela
Izinyathelo zokutholakala kwe-striatal D2 receptor (Bmax/Kd) beziphansi kakhulu ezifundweni ezikhuluphele kunezilawuli ezingakhuluphali (2.72±0.5 iqhathaniswa ne-3.14±0.40, ukuhlolwa kwe-Student=2.2, P<0.05). Ukuhlaziywa kwe-SPM okwenziwa ezifundweni ezikhuluphele ukuze kuhlolwe ukuhlobana phakathi kokutholakala kwe-D2 receptor kanye ne-regional brain glucose metabolism kubonise ukuthi kwakubalulekile kumaqoqo angu-4 ayegxile ku-(1) prefrontal kwesokunxele nakwesokudla (BA 9), CG (BA 32) kanye i-cortices yangemuva ye-orbitofrontal yesokunxele (BA 45):(2) i-prefrontal yesokunxele nesokudla (BA 10); (3) i-ventral cingulate gyrus (BA 25) kanye ne-medial orbitofrontal cortex (BA 11); kanye (4) ne-somatosensory cortex yangakwesokudla (BA 1, 2 kanye no-3) (Fig. 1, Table 1).Fig. 1 Amamephu obuchopho atholwe nge-SPM abonisa izindawo lapho ukuhlobana phakathi kokutholakala kwe-striatal D2 receptor kanye ne-brain glucose metabolism kwakubalulekile. Ukubaluleka kuhambisana no-P<0.005, okungalungisiwe, usayizi weqoqo>ama-voxel angu-100.
Ithebula 1
Izifunda zobuchopho lapho i-SPM iveze khona ukuhlobana okubalulekile (P<0.005) phakathi kokutholakala kwe-striatal D2 receptor kanye ne-glucose metabolismUkuhlaziywa okuzimele kokuhlobana phakathi kokutholakala kwe-DA D2 receptor ku-striatum kanye nezindlela ze-metabolic ezikhishwe kusetshenziswa i-ROI kuqinise okutholwe yi-SPM. Lokhu kuhlaziya kubonise ukuthi ukuhlobana kwakubalulekile ku-DLPFC yesobunxele nesokudla (ihambisana ne-BA 9 kanye ne-10), i-CG yangaphambili (ihambisana ne-BA 32 kanye ne-25) kanye ne-medial orbitofrontal cortex (i-BA 11 ephakathi). Iphinde yaqinisekisa ukuhlobana okubalulekile ne-somatosensory cortex elungile (i-postcentral parietal cortex) (Ithebula 2, Fig. 2).Ithebula lesi-2 lama-coefficients ahlotshaniswayo (amavelu angu-r) kanye namazinga okubaluleka (amanani angu-P) okuxhumana phakathi kwezilinganiso ze-DA D2 ye-striatal ukutholakala kwe-receptor (Bmax/Kd) kanye ne-regional metabolism metabolism ezifundweni ezikhuluphele kanye nasezilawulweniFig. 2 Ukuhlehla kwemithambeka phakathi kokutholakala kwesamukeli se-DA D2 (Bmax/Kd) kanye ne-glucose metabolism yesifunda (μmol/100 g/min) ezifundeni zangaphambili kanye naku-somatosensory cortex. Amanani alokhu kuhlotshaniswa aboniswa kuThebula 2.Ngaphezu kwalokho ukuhlaziywa okusebenzisa i-ROI kuphinde kwabonisa ukuhlobana okuphawulekayo ne-cortex ye-somatosensory kwesokunxele futhi kubonise ukuthambekela ku-gyrus angular kwesokudla kanye ne-caudate kwesokudla (Ithebula 2, Fig. 2). Ukuhlobana nenye i-cortical (i-occipital, i-temporal ne-lateral orbitofrontal cortex), i-subcortical (thalamus, i-striatum) nezifunda ze-cerebellar bekungabalulekile.Ngokuphambene, ezilawulweni ukuhlaziywa kwe-ROI kwembula ukuthi ukuphela kokuhlobana okubalulekile phakathi kokutholakala kwe-D2 receptor kanye ne-metabolism. ibisendaweni engakwesobunxele yangemuva. Kube khona ukuthambekela kokuhlobana ku-cortex ye-lateral orbitofrontal engakwesokudla kanye ne-angular gyrus engakwesokudla.
Ingxoxo
Lapha sibonisa ukuthi ezifundweni zokukhuluphala ngokweqile ze-DA D2 ukutholakala kwe-receptor kuhlotshaniswa nomsebenzi we-metabolic ezindaweni ezisekuqaleni (DLPFC, medial orbitofrontal cortex kanye ne-anterior CG). Lezi zifunda zonke zibe nomthelela wokulawula ukusetshenziswa kokudla naku-hyperphagia yabantu abakhuluphele (i-Tataranni et al., 1999, Tataranni kanye neDelParigi, i-2003). Sibonisa nokuhlobana okubalulekile kokutholwa kokudla emzimbeni somatosensory cortex (i-postcentral cortices) ebaluleke kakhulu ekuphathweni okwedlulele nasekulawulweni okungewona omese (izifunda ezingakwesobunxele kuphela). Ngenkathi sicubungule ukuxhumana kanye nezifunda zokuqala ukuhlangana ne-somatosensory cortex bekungukuthola okungalindelekile.
Inhlangano phakathi kwama-D2 receptors kanye ne-metabolism eyaphambili
Ubudlelwano obalulekile phakathi kokutholakala kwe-D2 receptors kanye ne-metabolism ezindaweni ezisekuqaleni kuhambelana nokutholakele kwethu kwezifundo eziluthwe izidakamizwa (i-cocaine, i-methamphetamine notshwala) esibonise ukuthi ukuncipha ezindaweni ze-D2 receptors kuhlotshaniswa nokuncipha kwemetabolism ezifundeni zokuqala ze-cortical ( Volkow et al., 1993b; Volkow et al., 2001; Volkow et al., 2007). Ngokufanayo kubantu ngabanye abasengozini enkulu yomndeni yokuphuza utshwala sabhala usoseshini phakathi kokutholakala kwe-D2 receptor kanye ne-predomal metabolism (Volkow et al., 2006). Kokubili ukukhuluphala kanye nokulutha ngokweqile kuyafana ukungakwazi ukubamba isimilo naphezu kokuqwashisa ngemiphumela yako emibi. Njengoba izifunda ezandulelayo zifakwa ezintweni ezahlukahlukene zokulawulwa kokuvimbela (UDalley et al., 2004) sibeka ukuthi ukutholakala okuphansi kwe-D2 receptor ku-striatum yezifundo ezikhuluphele (U-Wang et al., 2001) nakumamodeli wamagundane wokukhuluphala (Hamdi et al., 1992; UHuang et al., 2006; UThanos et al., 2008) angaba nesandla ekukhuluphaleni ngokwengxenye ngokushintshashintsha kweDA kwezifunda zangaphambili ezibamba iqhaza ekulawuleni ukuvimbela.
Okutholakele kubuye futhi kusikisele ukuthi ukulawulwa kwe-dopaminergic kwezifunda zangaphambili njengoba kuhlobene nengozi yokukhuluphala kungazindla nge-D2 receptors. Lokhu kuyahambisana nezifundo zofuzo, ezihlasele ngokuthe ngqo i-D2 receptor gene (TAQ-IA polymorphism), njengenye ebandakanyeka engcupheni yokukhuluphala (Fang et al., 2005; Pohjalainen et al., 1998; Bowirrat no-Oscar- IBerman, 2005). Ngaphezu kwalokho, i-polymorphism ye-TAQ-IA, ebonakala iphumela emazingeni aphansi e-D2 receptor ebuchosheni (striatum) (Ritchie kanye Noble, 2003; Pohjalainen et al., 1998; Jonsson et al., 1999) isanda kutholwa ihlotshaniswa ne ukwehla kwekhono lokuvimba izindlela zokuziphatha eziholela emiphumeleni emibi kanye nokusebenza okulimazayo kwezifunda zangaphambili (Klein et al., 2007). Ucwaningo olufana nalolo lubonisile ukuthi izilwane ezinamazinga aphansi we-D2 receptor ayaphoqeka kakhulu kunabantu abachitha nabo ngamazinga aphezulu we-D2 receptor level (Diking et al., 2007). Ngakho-ke okutholakele ocwaningweni lwethu kunikeza ubufakazi obengeziwe bokuthi ukuhlangana kwama-D2 receptors ngokulawulwa kokuvinjwa kanye nokuphoqelelwa kuhlanganiswa ngokwengxenye ngokuguqulwa kwabo kwezifunda zangaphambi. Kulokhu kuyajabulisa ukubona ukuthi izifundo zobuchopho bokuziphatha kobuchopho zibikile zanciphisa izindaba ze-greyex ku-preortalal cortex ezifundweni ezikhuluphele uma ziqhathaniswa nabantu abangenawo amandla (Pannacciulli et al., 2006).
Ukuhlangana phakathi kwama-receptors e-D2 ne-DLPFC kuthakazelisa kakhulu ngoba lesi sifunda sisanda kuthinteka ekuvimbeleni isenzo sangamabomu (I-Brass neHaggard, i-2007). Ubufakazi bokuthi umsebenzi we-neuronal wandulela ukuqaphela komuntu inhloso ngo-200-500 ms (Libet et al., 1983), kuholele ekutheni abanye bangabaze umqondo wentando "yokuzikhethela" ngemuva kwezenzo zokuzithandela futhi baphakamise ukuthi ukulawula kukhombisa amandla vimbela izenzo esingazifuni. Ngempela, kwaphakanyiswa ukuthi la mandla e-veto noma "inkululeko ngeke" kube yindlela esisebenzisa ngayo "inkululeko yokuzikhethela" (Mirabella, 2007). Endabeni yokukhuluphala umuntu angaveza ukuthi ukuvezwa kokudla noma izinkomba ezinesimo sokudla kuzoholela ekusebenzeni okungavunyelwe kokusebenza kwezinhlelo ze-neuronal ezibandakanyeka ekuthengeni nasekudleni ukudla nokuthi ukulawula kukhombisa amandla okuvimbela lezi zenzo zangamabomu zokufuna ukudla ukudla. Umuntu angabona ukuthi ukusebenza okungafanele kwe-DLPFC, okuvumela ukunqatshelwa kwezenzo eziholela emiphumeleni emibi, njengokudla lapho singalambile ngoba singafuni ukukhulisa isisindo, kungaholela ekuxebeni ngokweqile. Ukutholwa kokufaniswa okubonisa ukwehla okukhulu ekusebenzeni kwe-DLPFC ngemuva kokudla ezifundweni ezikhuluphele kunalezo ezisencane ezisekela lo mzwelo (Le et al., 2006).
Ukuhlangana phakathi kokutholakala kwe-D2 receptor kanye ne-medial orbitofrontal cortex (OFC) ne-anterior CG kuyahambisana nokuzibandakanya kwabo kulawulo lwesifiso sokudla (Pliquett et al., 2006). Kunezindlela eziningi umuntu angaphakamisa ngazo eziphazamisa ukusebenza kwe-dopaminergic kwe-OFC kanye ne-CG okwandisa ubungozi bokudla ngokweqile.
I-medial ye-OFC ibandakanyeka ekubalulekeni kwesasense kufaka phakathi inani lokudla (iRoll neMcCabe, 2007; Grabenhorst et al., 2007; Tremblay and Schultz, 1999) futhi ngaleyo ndlela ukusebenza kwayo kwesibili ekuvuselelekeni kokudla okwenziwe yi-DA kungaholela ekukhuthazeni okukhulu ukudla ukudla ngokungakwazi ukukuvumelanisa nakho. Ngaphezu kwalokho, ngoba ukuphazamiseka emsebenzini we-OFC kuphumela ekunciphiseni ukuhlangana kabusha kwezinhlangano ezifundile lapho kuqinisekiswa amandla okuqinisa (Gallagher et al., 1999) lokhu kungaholela ekudla ngokuqhubeka lapho inani lokudla selidonswa yi-satiety futhi lingachaza kungani ukulimala kwe-OFC kuhlotshaniswa nokuziphatha okuphoqayo kufaka phakathi ukudla ngokweqile (iButter et al., 1963, Johnson, 1971). Futhi i-OFC ibamba iqhaza ekufundeni izinhlangano zokuqinisa amandla okuqinisa kanye nesimo (i-Schoenbaum et al., 1998, Hugdahl et al., 1995) futhi ngenxa yalokho ibambe iqhaza ekondleni okukhonjelwe i-cue elicited (Weingarten, 1983). Lokhu kufanelekile ngoba izimpendulo ezifakwe kukudla kokudla kungenzeka zibe nomthelela ekudla kakhulu kungakhathalekile amasiginali endlala (Ogden and Wardle, 1990).
I-dorsal CG (BA 32) ithinteka ekuvinjelweni kokuvinjelwa ezimweni ezifuna ukubhekwa kokusebenza futhi ngaleyo ndlela umsebenzi wayo ophazamisayo kanye nowe-DLPFC lapho ixhumana khona (i-Gehring ne-Knight 2000) kungenzeka iqhubeke nokulimaza amandla omuntu omkhulu ngokweqile. ukuvimbela ukuthambekela kokudla ngokweqile. I-ventral CG (BA 25) ifakwa umfutho ekuphenduleni izimpendulo ezingokomzwelo zesisulu sokukhuthazeka (ukuvuza kanye nokuphindiselela) (Elliott et al., 2000) kanye nezifundo zokucabanga okukhombisa ukuthi i-BA 25 icushiwe ngemivuzo yemvelo nezidakamizwa (uBreaker et al., 1997, uFrancis et al., 1999; Berns et al., 2001). Ngakho-ke ukuhlangana okungalungile phakathi kwe-D2 receptors kanye nokuthambekela kokudla lapho kuvezwa imizwa emibi esike sayibika kulawulo olunempilo (iVolkow et al., 2003) ingalungiswa ngokuguqulwa kwe-BA 25.
Ukuhlangana phakathi komsebenzi we-metabolic ezifundeni ezisekuqaleni kanye nama-D2 receptors kungakhombisa ukuqagela ku-cortex yangaphambili kusuka ku-ventral kanye ne-dorsal striatum (iRay ne-Intengo, i-1993), okuyizifunda ezifaka umfutho ekuqiniseni nasemiphumeleni yokudla (Koob and Bloom, 1988) kanye / noma kusuka endaweni yangaphakathi ye-ventral tegmental (VTA) ne -antiantia nigra (SN), okuyizinto eziqokiwe ze-DA eziphambili ezokwenza i-striatum (Oades and Halliday, 1987). Kodwa-ke, i-cortex yokuqala iphinda ithumele ukuqagela ku-striatum ukuze inhlangano ikwazi ukukhombisa ukulawulwa kwangaphambili komsebenzi we-DA wezokwenziwa (uMurase et al., 1993).
Ezilawulweni ezingezona ezinamafutha okuhlobana phakathi kwe-D2 receptor kanye ne-metabolism yangaphambilini bekungasho lutho. Ekutholakalweni kwangaphambilini sasikhombise ukuhlangana okubalulekile phakathi kwe-D2 receptor kanye ne-metabolism yangaphambili ezintweni eziwumlutha ngokutholakala okuphansi kwe-D2 receptor kodwa hhayi kwizilawuli (Volkow et al., 2007)Kodwa-ke, ukuqhathanisa kokuhlobana phakathi kwama-onese namaqembu okulawula bekungabalulekanga, okubonisa ukuthi cishe akunakwenzeka ukuthi ubudlelwane phakathi kwe-D2 receptors kanye ne-prelocal metabolism buyingqayizivele yokukhuluphala (noma umlutha ngokwe Volkow et al., 2007). Kungenzeka ukuthi ukuhlangana okunamandla okubonwe kubantu abakhuluphele kubonise uhla olukhulu lwezinyathelo ze-striatal D2 receptor ineseese (Bmax / Kd uhla 2.1-3.7) kunasezifundweni zokulawula (Bmax / Kd uhla 2.7-3.8).
Ekuhumusheni lokhu okutholakele kubalulekile ukuthi futhi ucabangele ukuthi i- [11C] raclopride is radiotracer e-D2 receptors ithinta i-endo native DA (Volkow et al., 1994) futhi ngaleyo ndlela ukuncipha kokutholakala kwe-D2 receptor kwizifundo ezikhuluphele kungakhombisa okuphansi amazinga we-receptor noma ukwanda kokukhishwa kwe-DA. Izifundo ezisezingeni eliphakeme kumamodeli wezilwane ezikhuluphele zibhale ukuncishiswa ekuqoqweni kwama-D2 receptors (Thanos et al., 2008), ophakamisa ukuthi ukuncipha kwezihloko ezikhuluphele kubonisa ukwehla kwamazinga we-D2 receptor.
Ukuhlangana phakathi kwe-D2R ne-somatosensory cortex
Sasingenayo i- "aoriori" yokuqagela ukuhlangana phakathi kwama-D2 receptors kanye ne-metabolism ku-somatosensory cortex. Uma kuqhathaniswa nezifunda ezingaphambili noma zesikhashana kuncane kakhulu okwaziwayo ngomthelela we-DA ku-parietal cortex. Ebuchosheni bomuntu ukugxila kwama-D2 receptors kanye ne-D2 mRNA ku-parietal cortex ngenkathi kuphansi kakhulu kunezindawo ezingaphansi kwe-subcortical kulingana nokuthi kubikwe ku-frontal cortex (Suhara et al., 1999; Mukherjee et al., 2002; Hurd et al., 2001). Yize kunemibhalo elinganiselwe ngendima ye-somatosensory cortex ekudleni nasekukhuluphaleni. Ucwaningo lokucabanga lubike ukwenziwa kwe-cortex yesikhashana ezifundweni zesisindo esijwayelekile ngokuvezwa kwezithombe ezibukwayo zokudla okuphansi kwe-caloric (UKillgore et al., 2003) nangokusutha (UTataranni et al., 1999), futhi besikhombise ukuphakama kwesisekelo semetabolism ku-cortex ye-somatosensory ezifundweni ezikhuluphele kakhulu (U-Wang et al., 2002). Futhi ucwaningo lwakamuva lubike ukuthi kubantu abakhuluphele kakhulu abane-leptin yokushoda kokuphathwa kwe-leptin bajwayele isisindo somzimba wabo futhi banciphisa ukusebenza kobuchopho ku-parietal cortex ngenkathi bebuka izinto ezihlobene nokudla (I-Baicy et al., 2007). Ukuxhuma okusebenzayo phakathi kwe-striatum ne-somatosensory cortex kusanda kufakazelwa ubuchopho bomuntu ngokucwaninga kwe-meta-analysis kwizifundo ze-imaging ezisebenzayo eziyi-126, ezibhale ukusebenzisana kokusebenza kwecortex yesomososory naleyo ye-dorsal striatum (I-Postuma ne-Dagher, i-2006 ). Kodwa-ke, kusukela ekuhlanganisweni esifundweni sethu asikwazi ukuthola ukuqondiswa kwenhlangano; ngakho-ke asikwazi ukunquma ukuthi ukuhlangana nama-receptors e-D2 kukhombisa ukuguquguquka kwe-DA kwe-somatosensory cortex kanye / noma nethonya le-somatosensory cortex ekutholakaleni kwe-D2 receptor etholakalayo. Ngempela kunobufakazi obanele bokuthi i-somatosensory cortex inomthelela ekusebenzeni kobuchopho be-DA kubandakanya ukukhishwa kwe-striatal DA (Huttunen et al., 2003; Rossini et al., 1995; Chen et al., 2007). Kukhona nobufakazi bokuthi i-DA ilungisa i-somatosensory cortex ebuchosheni bomuntu (Kuo et al., 2007). Ngenxa yokuthi ukugqugquzelwa kwe-DA kukhombisa ubuqili futhi kusize isimo (UZink et al., 2003, uKelley, 2004), ukushintshashintsha kwe-DA kwempendulo ye-somatosensory cortex ekudleni kungenzeka kudlale indima ekwakhiweni kwenhlangano enesimo phakathi kokudla nemvelo ehlobene nokudla imikhondo kanye nenani eliqinisiwe lokuqina lokudla okwenzeka ekukhuluphaleni (U-Epstein et al., 2007).
Imikhawulo yokutadisha
Umkhawulo kulolu cwaningo ukuthi asizitholanga izindlela ze-neuropsychological futhi ngakho-ke asikwazi ukuhlola ukuthi ngabe umsebenzi owenziwa ezifundeni zangaphambili uhlotshaniswa nezindlela zokuziphatha zokulawula kokuqonda kulezi zifundo ezinamafutha. Yize izifundo ezenziwa yi-neuropsychological on obesity limited kanti okutholakele kudideka ngenxa yezinkinga zezokwelapha zokukhuluphala (okusho isifo sikashukela kanye nomfutho wegazi ophakeme), kunobufakazi bokuthi ngezifundo ezikhuluphele inhibitory control zingaphazamiseka. Ngokuqondile, uma kuqhathaniswa nabantu abajwayelekile besisindo, izifundo ezikhuluphele zenza ukukhetha okuncane okunenzuzo, okukuthola okuhambisanayo nokulawulwa kokuvinjezelwa kokuvinjwa kokungasebenzi kanye nokusebenza kahle kwangaphambi kokuqala (Pignatti et al., 2006). Ngaphezu kwalokho amanani wokushoda okubonisa ukungasebenzi kahle kwe-hyperacaction disorder (ADHD), okubandakanya ukuphazamiseka ekuxhamazelweni, aphakanyiswa ngabantu abakhuluphele (i-Altfas, 2002). Ngokufanayo ukushukumisela kuye kwaxhunyaniswa ne-BMI ephezulu kwezinye izakhamuzi (Fassino et al., 2003) nasezilawulweni ezinempilo i-BMI nayo ihlotshaniswe nokusebenza emisebenzini yemisebenzi ephakeme eqondisayo yokulamula (Gunstad et al., 2007).
Futhi ngenkathi kuleli phepha sigxila endimeni edalulwa yi-cortex yokuqala ekuphatheni okunganqamuki nasekuziphoqeleleni siyabona ukuthi i-cortex yangaphambili ibandakanyeka emisebenzini ehlukahlukene yengqondo iningi labo elingaphazamiseki ezifundweni ezikhuluphele (Kuo et al., I-2006, uWolf et al., 2007). Kungenzeka ukuthi imisebenzi ye-preortalal cortex efaka isandla ekukhuluphiseni yizo ezibuthakathaka ekushintsheni kwe-DA ngemigudu yangaphambi kokuqala (iRobbins, 2007; Zgaljardic et al., 2006).
Ukuthambekela kokusebenza kwangaphambili noma ukukhubazeka komsebenzi wokuphatha akucacisanga ukukhuluphala. Impela ukungajwayelekile kokuphambi kwemetabolism kanye nokukhubazeka ekusebenzeni okuphezulu kubhalwe ezinkingeni eziningi ezahlukahlukene kubandakanya lezo ezinokubandakanyeka kwe-dopaminergic njengokulutha izidakamizwa, i-schizophrenia, isifo sikaParkinson kanye ne-ADHD (Volkow et al., 1993b; UGur et al., 2000; URobbins, 2007; UZgaljardic et al., 2006).
Okunye ukukhawulelwa ukuthi ukulungiswa okulinganiselwe kwendawo ye-PET [11C] indlela ye-raclopride akusivumelanga ukukala ukutholakala kwe-D2 receptor ezindaweni ezincane zobuchopho ekubalulekeni kokuziphatha okuhlobene nokudla okufana ne-hypothalamus.
Okokugcina ukuxhumeka akusho ukuthi izinhlangano ezibandakanyekayo futhi izifundo ezengeziwe ziyafuneka ukuze kuhlolwe imiphumela yokuphazamiseka komsebenzi wobuchopho be-DA ekusebenzeni phambili kwezifundo ezikhuluphele.
Isifinyezo
Lolu cwaningo lukhombisa ubudlelwane obonakalayo ezifundweni ezicebile phakathi kwe-D2 receptors ku-striatum nomsebenzi ku-DLPF, medical OFC kanye ne-CG (izifunda zobuchopho ezifakwe kulawulo lwe-inhibitory, isizalo se-salience kanye nokuhlangana ngokomzwelo futhi ukuphazamiseka kwabo kungaholela ekuziphatheni okuphoqayo nokuphoqayo), okuthi kuphakamisa ukuthi lokhu kungaba enye yezindlela ama-D2 receptors asemafutheni angaba nomthelela ngazo ekukhuluphiseni nasekufutheni ngokweqile. Ngaphezu kwalokho futhi sibhala ukuhlangana okubalulekile phakathi kwe-D2 receptors kanye ne-metabolism ku-cortex ye-somatosensory engalingisa izakhiwo zokuqinisa (i-Epstein et al., 2007) futhi kufanele ukuthi kuqhubeke uphenyo.
Ukuvuma
Sibonga uDavid Schlyer, David Alexoff, Paul Vaska, Colleen Shea, Youwen Xu, Pauline Carter, Karen Apelskog, noLinda Thomas ngeminikelo yabo. Lolu cwaningo lwalusekelwa yi-NIH's Intramural Research Program (NIAAA) kanye ne-DOE (DE-AC01-76CH00016).
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