Batho ba tlaase ba nang le bokooa ba Dopamatal D2 ba kopane le Prefrontal Metabolism Lihloohong Tse Bohloko: Lintho Tse ka Etsanghalang Tse ka Etsang (2008)

LIQOLE: Tlhahlobo ena mabapi le botenya, e tsepamisitsoeng ho li-receptor tsa dopamine (D2) le kamano ea tsona ho frontal lobe e sebetsang. Patlisiso ena, e etsoang ke hlooho ea NIDA, e bonts'a hore likelello tsa batho ba jang lithethefatsi tse ling tse tlisoang ke lithethefatsi li tšoana le tsa batho ba lemaletseng lithethefatsi mechineng e 'meli e hlahlobiloeng. Joalo ka lithethefatsi, lithethefatsi li na le li-receptor tsa D2 tse tlase, le hypofrontality. Li-receptor tsa D2 tse tlase ke eona ntho e ka sehloohong ho desensitization (palo ea karabelo ea thabo) ea potoloho ea moputso. Hypofrontality e bolela metabolism e tlase ka pele ho cortex, e amanang le taolo e mpe ea tšusumetso, maikutlo a eketsehang, le kahlolo e mpe ea litlamorao. Ho bonahala ho na le kamano pakeng tsa li-receptor tse tlase tsa D2 le tšebetso e tlase ea li-lobes tsa pele. Ka mantsoe a mang, ho fetelletsa lintho ho lebisa ho fokotseheng ha li-receptor tsa D2 tse amang li-lobes tse ka pele./em>

HO ITHUTA KA TSOHLE: Li-receptor tsa Dopamine Striatal D2 tse tlase li kopantsoe le "Metabolism ea Pele ho Lintho"

Neuroimage. 2008 Mphalane 1; 42 (4): 1537-1543.
E phatlalalitsoe online 2008 June 13. Doi: 10.1016 / j.neuroimage.2008.06.002.

Nora 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 le Kith Pradhanc
Setsi sa Naha sa Tlhekefetso ea Lithethefatsi, Bethesda MD 20892, USA
b Setsi sa Naha sa Tlhekefetso ea Joala le Joala, Bethesda MD 20892, USA
c Lefapha la Bongaka Brookhaven National Laborator, Upton NY 11973, USA
d Lefapha la Diagnostic Radiology, Yale University School of Medicine New Haven, CT 06520-8042, USA
* Sengoli se lumellanang. Setsi sa Naha sa Tlhekefetso ea Lithethefatsi, 6001 Executive Boulevard, Kamore ea 5274, Bethesda, MD 20892, USA. Fekse: + 1 301 443 9127. Liaterese tsa lengolo-tsoibila: Imeile: [imeile e sirelelitsoe] Imeile: [imeile e sirelelitsoe] (ND Volkow).

inahaneloang

Karolo ea Dopamine taolong ea thibelo e tsebahala hantle mme pherekano ea eona e ka tlatsetsa mathateng a boitšoaro a ho se laole joalo ka botenya. Leha ho le joalo, mochini o fokolisang dopamine neurotransmission o sitisa taolo ea thibelo ha o utloisisoe hantle. Pejana re ne re ngotse phokotso ea li-receptor tsa dopamine D2 lithutong tse feteletseng tse mpe. Ho lekola hore na phokotso ea li-receptor tsa dopamine D2 li amahanngoa le ts'ebetso ea libaka tsa pele tsa boko tse amehang taolong ea thibelo re ile ra lekola kamano lipakeng tsa ho fumaneha ha dopamine D2 receptor ho striatum le metabolism ea methapo ea boko (letšoao la ts'ebetso ea boko) lithutong tse leshome tse feteletseng tse feteletseng (BMI> 40 kg / m2) mme a e bapisa le eo ho taolo tse leshome le metso e 'meli tse sa nonneng. PET e sebelisitsoe le [11C] raclopride ho lekola li-receptor tsa D2 le [18F] FDG ho lekola metabolism ea tikoloho ea tsoekere. Lithutong tse feteletseng ho fumaneha ha li-receptor tsa D2 ho ne ho le tlase ho feta taolo mme ho ne ho amana hantle le metabolism ho dorsolateral prefrontal, medial orbitofrontal, anterior cingulate gyrus le somatosensory cortices. Lits'ebetsong tsa taolo le metabolism ea pele e ne e se ea bohlokoa empa papiso le tse lihloohong tse nonneng e ne e se tsa bohlokoa, tse sa lumelleng ho fana ka mekhatlo e ikhethile ho nona haholo. Mekhatlo lipakeng tsa li-receptors tsa striatal D2 le metabolism ea pele lithutong tse feteletseng e fana ka maikutlo a hore ho fokotseha ha li-receptor tsa D2 tse ka tsoaloang ho ka kenya letsoho ho jang ho feta tekano ka ho feto-fetoha ha bona ha litsela tsa pelehi, tse nkang karolo ho taolo ea thibelo le boits'oaro ba boiphihlelo. Kamano lipakeng tsa li-receptor tsa D2 tsa striatal le metabolism ho li-cortices tsa somatosensory (libaka tse sebetsanang le ho ba bonolo) li ka theha o mong oa mekhoa eo ka eona dopamine e laolang matlafatso ea lijo.

Mantsoe a bohlokoa: Orbitofrontal cortex, Cingulate gyrus, Dorsolateral pele, ba tsamaisang thepa ea Dopamine, Raclopride, PET

Keketseho ea botena le mafu a amanang le metabolic a bonoang lilemong tse fetang tse leshome tse fetileng e hlahisitse matšoenyeho a hore haeba e sa laoloe sena e ka ba tšokelo ea pele ea bophelo bo botle ba sechaba bakeng sa 21st century (Sturm, 2002). Leha mabaka a mangata a kentse letsoho ho eketseheng ha botenya bona keketseho ea phapang le phihlello ea lijo tse fumanehang habonolo e ka se nyenyefatsoe (Wardle, 2007). Kaha ho fumaneha ha lijo le mefuta e mengata ho eketsa monyetla oa ho ho ja ho feta tekano (hlahloba Wardle, 2007) ho fihlella habonolo ha lijo tse ipiletsang ho hloka tlhoko ea khafetsa ea ho thibela takatso ea ho e ja (Berthoud, 2007). Tekanyo eo batho ka bomong ba fapaneng ka eona ho bokhoni ba bona ba ho thibela likarabo tsena le ho laola hore na ba ja hakae ho ka fokotsa kotsi ea bona ea ho ja ho feta tekano libakeng tsa rona tse nang le lijo tse ngata (Berthoud, 2007).

Re ne re bonts'itse hore ho batho ba phetseng hantle D2 fumaneha ka har'a mekhoa ea boikoetliso ea mekhoa ea ho ja (Volkow et al., 2003). Haholo-holo tloaelo ea ho ja ha e pepesetsoa maikutlo a mabe e ne e amana hampe le ho fumaneha ha D2 receptor (tlase D2 receptors e ne e le monyetla o holimo oo motho a neng a ka o ja haeba a sithabetse maikutlo). Ntle le moo, thutong e fapaneng, re bonts'itse hore lithuto tsa moriana o feteletseng (BMI> 40) li ne li le tlase ho feta tlhaelo e tloaelehileng ea D2 receptor mme phokotso tsena li ne li lekana le BMI ea bona (Wang et al., 2001). Liphumano tsena li re lebisitse ho hatisa hore ho fumaneha ha D2 e tlase ho ka beha motho kotsing ea ho nona. Ha e le hantle sena se lumellana le lipatlisiso tse bonts'ang hore ho thibela li-receptor tsa D2 (meriana ea antipsychotic) ho eketsa takatso ea lijo mme ho hlahisa kotsi ea botenya (Allison et al., 1999). Leha ho le joalo, mekhoa eo ho fumaneha ha li-receptor tsa D2 tse fokolang e eketsang kotsi ea ho nona ha e utloisisehe hantle.

Haufinyane ho bonts'itsoe hore taolong e phetseng hantle liphatsa tsa lefutso tsa lefutso la D2 receptor li ne li amahanngoa le boits'oaro ba taolo ea thibelo (Klein et al., 2007). Haholo-holo, batho ba nang le mofuta o fapaneng oa liphatsa tsa lefutso o amanang le polelo e tlase ea D2 ba ne ba na le taolo e nyane ho feta batho ba nang le mofuta o fapaneng oa liphatsa tsa lefutso o amanang le polelo e phahameng ea D2 mme likarabo tsena tsa boits'oaro li ne li amahanngoa le liphapang tsa ts'ebetso ea cingulate gyrus (CG) le preortal ea dorsolateral cortex (DLPFC), e leng libaka tsa boko tse kentsoeng likarolong tse fapaneng tsa taolo ea thibelo (Dalley et al., 2004). Sena se re lebisitse ho nahana hape ka monyetla oa hore kotsi e kholo ea ho ja ho feta lithutong tse nang le phihlello e tlase ea D2 e ​​kanna ea tsamaisoa ke taolo ea DA ea DLPFC le libaka tse ka pele ho naha, tse bontšitsoeng hore li nka karolo ho thibeleng litloaelo tse sa lokelang tsa boits'oaro (Mesulam , 1985; Le Doux, 1987; Goldstein le Volkow, 2002). Kahoo re ile ra etsa tlhahlobo ea bobeli ho data e tsoang lihloohong tse neng li kile tsa hiroa pejana e le karolo ea lithuto ho lekola liphetoho ho li-receptors tsa D2 (Wang et al., 2001) le metabolism ea tsoekere bokong ka botenya (Wang et al., 2002) le data ho tsoa lilemo li tsamaellana. Khopolo-taba ea rona ea ho sebetsa e ne e le hore ho fumaneha ha li-receptor tsa D2 lihloohong tse nang le botenya haholo ho tla amahanngoa le ts'ebetso e sitisang libaka tsa pele.

Bakeng sa thuto ena morbidly o feteletseng lithuto le lithuto tse se nang botenya li ne li lekotsoe ka Positron Emission Tomography (PET) hammoho le [11C] raclopride ho lekanya DA D2 receptors (Volkow et al., 1993a) le [18F] FDG ho lekanya boko glucose metabolism (Wang et al., 1992). Re kholoa hore li-receptors tsa D2 tsa DA li ka amahanngoa le metabolism libakeng tsa pele (DLPFC, CG le orbitofrontal cortex).

Method

Lihlooho
Lihlooho tse leshome tse nonneng haholo (basali ba 5 le banna ba 5, li bolela lilemo tse 35.9 ± 10) tse nang le boima ba 'mele bo boima (BMI: boima ba lik'hilograma tse arotsoeng ka sekwere sa bophahamo ba limithara) tsa 51 ± 5 kg / m2 li khethiloe letamong ea lihlooho tse nonneng tse arabetseng papatso. Ho ile ha khethoa lithuto tse leshome le metso e 'meli tse sa nonneng (basali ba 6 le banna ba 6, ho bolela hore ba lilemo li 33.2 ± 8) ba nang le BMI e bolelang ea 25 ± 3 kg / m2 bakeng sa papiso. Barupeluoa ba ile ba hlahlojoa ka hloko ka nalane e qaqileng ea bongaka, tlhahlobo ea 'mele le methapo ea pelo, EKG, liteko tsa mali tse tloahelehileng, le chefo ea moroto bakeng sa lithethefatsi tsa psychotropic ho netefatsa hore li phethahatsa litekanyetso tsa ho kenyeletsoa le ho khetholla. Mekhoa ea ho kenyelletsa e ne e le: 1) bokhoni ba ho utloisisa le ho fana ka tumello e nang le tsebo; 2) BMI> 40 kg / m2 bakeng sa lithuto tse nonneng le BMI <30 kg / m2 bakeng sa lithuto tsa papiso le 3) ea lilemo li 20-55. Mekhoa ea ho khetholla e ne e le: (1) lefu la kelello la hajoale kapa la nakong e fetileng le / kapa methapo ea methapo, (2) ts'itiso ea hlooho le ho lahleheloa ke tsebo e fetang 30 min, (3) khatello ea kelello, lefu la tsoekere le maemo a bongaka a ka fetolang ts'ebetso ea bokong, (4) ts'ebeliso ea meriana ea anorexic kapa ea ho buoa bakeng sa ho theola boima ba 'mele likhoeling tse 6 tse fetileng, (5) meriana kapa litlhare tse fanoang ke ngaka libekeng tse 4 tse fetileng, (6) nalane ea khale kapa ea hajoale ea ts'ebeliso e mpe ea joala kapa lithethefatsi (ho kenyeletsoa le ho tsuba koae). Bafo ba ile ba laeloa hore ba khaotse ho sebelisa litlhare kapa litlatsetso tsa phepo e ntle bekeng e le 1 pele ho scan. Ho ile ha etsoa liteko tsa pele ho skena mochini ho netefatsa ho ba sieo ha ts'ebeliso ea lithethefatsi ea psychoactive. Litumellano tse saennoeng tse saenneng li fumanoe ho tsoa ho lithuto pele ho ho nka karolo joalo ka ha ho amohetsoe ke Boto ea Setsi ea Tlhahlobo ho Laboraro la Naha la Brookhaven.PET imaging
Lits'oants'o tsa PET li entsoe ka CTI-931 (Computer Technologies, Incorporate, Knoxville, Tenn.) Tomograph (resolution 6 × 6 × 6.5 mm FWHM, 15 slices) with [11C] raclopride and [18F] FDG. Lintlha mabapi le lits'ebetso tsa ho beha maemo, arterial le venous catheterization, quanifying ea radiotracer le transmission le scans screen li phatlalalitsoe bakeng sa [11C] raclopride (Volkow et al., 1993a), and for [18F] FDG (Wang et al., 1992) . Ka bokhutšoanyane bakeng sa morusu oa [11C], li-scans tse matla li ile tsa qalisoa hang ka mor'a hore iv ente ea 4-10 mCi (tšebetso e khethehileng> 0.25 Ci / μmol ka nako ea ente) bakeng sa kakaretso ea 60 min. Bakeng sa [18F] FDG, scan e 'ngoe ea emissions (20 min) e nkuoe 35 min kamora ho entoa ka iv iv ea 4-6 mCi ea [18F] FDG. Sekala se entsoe ka letsatsi lona leo; the [11C] scanlopride scan e ile ea etsoa pele 'me ea lateloa ke [18F] FDG, e ileng ea kenngoa 2 h kamora [11C] raclopride ho lumella ho bola ha 11C (halofo ea bophelo ea 20 min. Nakong ea lithuto li ne li lula li robetse ka har'a kh'amera ea PET mahlo a bona a bulehile; kamore eo e ne e fifalitsoe ke lerata 'me lerata le lula le bonyane. Mooki o ile a lula le lithuto nakong ea ts'ebetso eohle ho netefatsa hore sehlooho ha se robala nakong ea thuto.

Tlhatlhobo ea litšoantšo le ya data
Mekha ea libaka tse khahlisang (ROI) ho litšoantšo tsa [11C] ea baeti ba marang-rang e fumanoe bakeng sa striatum (caudate le putamen) le bakeng sa cerebellum. Li-ROI li ne li khethiloe qalong ka har'a scan ninemanga (tšebetso ho tloha 10-60 min bakeng sa [11C] raclopride), 'me ka nako eo li ne li fuoa liteko tse matla joalo ka ha ho hlalositsoe pele (Volkow et al., 1993a). Ketsahalo ea nako ea curlopride ea [11C] ka har'a striatum, le cerebellum le nako eo li-tracer tse sa fetoheng ho plasma li sebelisitsoeng ho bala li-volumes (DV) li sebelisa mokhoa oa tlhahlobo ea litšoantšo bakeng sa sistimi e fetohelang (Logan Plots) (Logan et al. ., 1990). Paramente Bmax / Kd, e fumanoeng e le karo-karolelano ea DV ho striatum ho eo e leng cerebellum (DVstriatum / DVcerebellum) minus 1, e ne e sebelisoa e le mohlala oa paramente ea DA D2 receptor. Paramethara ena ha e na taba le phetoho ho phallo ea mali a khubung (Logan et al., 1994).

Ho lekola likamano lipakeng tsa ho fumaneha ha li-receptor tsa D2 le metabolism ea tsoekere ea boko re ile ra kopanya likhokahano re sebelisa Statistical Parametric Mapping (SPM) (Friston et al., 1995). Ka mor'a moo, liphetho tsa SPM li ile tsa tiisoa le libaka tsa thahasello tse ikemetseng (ROI); ke hore, libaka tse fumanoeng ho sebelisoa template e neng e sa tataisoe ke likhokahano tse fumanoang ho SPM. Bakeng sa litlhahlobo tsa SPM, litšoantšo tsa mehato ea metabolic li ile tsa tloaeleha sebakeng ho sebelisoa template e fanoeng ka har'a sephutheloana sa SPM 99, 'me hamorao sa lokisoa ka kernel ea 16 mm isotropic Gaussian. Bohlokoa bakeng sa likamano bo ne bo behiloe ho P <0.005 (e sa lokisoang, li-voxels tsa 100) 'me limmapa tsa lipalo-palo li ne li koahetsoe ka setšoantšo sa sebopeho sa MRI.Bakeng sa tlhahlobo ea ROI re ile ra ntša libaka ka ho sebelisa template, eo re neng re e hatisitse pele (Wang et al., 1992). Ho tsoa ho template ena re khethile li-ROI bakeng sa medial le lateral orbitofrontal cortex (OFC), anterior cingulate gyrus (CG) le dorsolateral prefrontal cortex (DLPFC) eo re neng re nahana ka eona "priori" kamano le li-receptor tsa DA D2, ROIs bakeng sa caudate. le putamen, tseo e neng e le li-ROI e ne e le li-receptor tsa D2 tse bolaeang li ile tsa lekanngoa, 'me li-ROI ka parietal (somatosensory cortex le angular gyrus), temporal (e phahameng le e tlaase ea temporal gyri le hippocampus), le occipital cortices, thalamus le cerebellum, tse khethiloeng e le neutral ROIs.Pearson litlhahlobo tsa khokahano ea motsotso oa sehlahisoa li entsoe lipakeng tsa ho fumaneha ha li-receptor tsa D2 ho striatum le mehato ea metabolic ea tikoloho. Boemo ba bohlokoa bakeng sa likamano pakeng tsa li-receptor tsa D2 le metabolism ea libaka ho tloha ho ROI e behiloe ho P <0.01 le litekanyetso tsa P <0.05 li tlalehoa e le mekhoa. Liphapang tsa likamano pakeng tsa lihlopha li ile tsa lekoa ho sebelisoa tlhahlobo ea kakaretso ea liketsahalo tse sa tšoaneng bakeng sa ho fokotseha le bohlokoa bo behiloeng ho P <0.05.

Results

Mehato ea ho fumaneha ha li-receptor tsa striatal D2 (Bmax/Kd) e ne e le tlase haholo lithutong tse batenya ho feta taolong e sa fetelletseng (2.72 ± 0.5 khahlano le 3.14 ± 0.40, Teko ea Seithuti = 2.2, P <0.05). Tlhahlobo ea SPM e entsoeng ho batho ba batenya ho lekola kamano pakeng tsa ho fumaneha ha li-receptor tsa D2 le metabolism ea glucose ea boko e bontšitse hore e bohlokoa ho lihlopha tsa 4 tse neng li tsepamisitse maikutlo ho (1) ka ho le letšehali le ka ho le letona (BA 9), CG (BA 32) le le letšehali lateral orbitofrontal cortices (BA 45):(2) le letšehali le le letona prefrontal (BA 10); (3) ventral cingulate gyrus (BA 25) le medial orbitofrontal cortex (BA 11); le (4) tokelo ea somatosensory cortex (BA 1, 2 le 3) (Setšoantšo sa 1, Lethathamo la 1) . Limmapa tse 1 tsa boko tse fumanoeng ka SPM tse bonts'ang libaka tseo ho tsona likamano lipakeng tsa ho fumaneha ha li-receptor tsa D2 le metabolism ea tsoekere ea boko li ne li le bohlokoa. Bohlokoa bo lumellana le P<0.005, e sa lokisoang, boholo ba lihlopha> 100 voxels.

Lethathamo 1
Libaka tsa boko moo SPM e senotseng likamano tsa bohlokoa (P <0.005) lipakeng tsa ho fumaneha ha li-receptor tsa striatal D2 le metabolism ea glucoseTlhahlobo e ikemetseng bakeng sa likamano lipakeng tsa ho fumaneha ha li-receptor tsa DA D2 ho striatum le mehato ea metabolic e ntšitsoeng ho sebelisoa ROI e netefalitse liphuputso tsa SPM. Tlhahlobo ena e bontšitse hore likamano li ne li le bohlokoa ho DLPFC e letšehali le e nepahetseng (e tsamaellanang le BA 9 le 10), anterior CG (e lumellanang le BA 32 le 25) le medial orbitofrontal cortex (medial BA 11). E ile ea boela ea tiisa kamano ea bohlokoa le cortex e nepahetseng ea somatosensory (postcentral parietal cortex) (Letlapa la 2, Fig. 2) . Letlapa la 2 Correlation coefficients (r litekanyetso) le maemo a bohlokoa (P boleng) bakeng sa likamano pakeng tsa mehato ea striatal DA D2 ho fumaneha ha li-receptor (Bmax/Kd) le metabolism ea boko ba sebaka lithutong tse nonneng le taolong 2 Matsoapo a ho fokotseha pakeng tsa ho fumaneha ha li-receptor tsa DA D2 (Bmax/Kd) le metabolism ea glucose ea tikoloho (μmol/100 g/min) libakeng tsa prefrontal le ho somatosensory cortex. Litekanyetso tsa likamano tsena li bontšoa ho Lethathamo la 2. Ho phaella moo tlhahlobo e sebelisang ROI e ile ea boela ea bontša likamano tse kholo le cortex ea somatosensory e ka letsohong le letšehali 'me ea bontša mokhoa o nepahetseng oa gyrus le caudate e nepahetseng (Letlapa la 2, Setšoantšo sa 2). Likamano le libaka tse ling tsa cortical (occipital, temporal le lateral orbitofrontal cortex), subcortical (thalamus, striatum) le libaka tsa cerebellar li ne li se tsa bohlokoa. Ka lehlakoreng le leng, litaolong tsa tlhahlobo ea ROI li senoletse hore kamano e le 'ngoe feela ea bohlokoa pakeng tsa ho fumaneha ha D2 receptor le metabolism. e ne e le ka ho le letšehali postcentral gyrus. Ho ne ho e-na le mokhoa oa ho hokahanya cortex ea lateral orbitofrontal le gyrus e nepahetseng ea angular.

Puisano

Mona re bonts'a hore lithutong tse fumanehang ka moriti oa ho sebelisa li-DA D2 ho fumaneha ha li-receptor ho ne ho amana le ts'ebetso ea metabolic libakeng tsa pele (DLPFC, medial orbitofrontal cortex le anterior CG). Libaka tsena kaofela li bile le tšusumetso ho laoleng tšebeliso ea lijo le hyperphagia ea batho ba batenya haholo (Tataranni et al., 1999, Tataranni le DelParigi, 2003). Re boetse re bonts'a khokahano ea bohlokoa ea metabolism ho somatosensory cortex (postcentral cortices) e neng e le bohlokoa haholo lits'ebetsong tse feteletseng le tse sa laoloeng haholo (libaka tse setseng feela). Le ha re ne re kentse likamano tsa rona hantle le libaka tsa pele ho kamano ea bona le somatosensory cortex e ne e le litholoana tse sa lebelloang.

Kamano pakeng tsa li-receptor tsa D2 le metabolism ea pele

Kopano ea bohlokoa pakeng tsa ho fumaneha ha li-receptor tsa D2 le metabolism libakeng tse tlang pele e lumellana le seo re se fumaneng pele lithutong tse lemaletseng lithethefatsi (cocaine, methamphetamine le joala) tseo re bonts'itseng hore phokotso ho li-receptor tsa D2 li ne li amana le ho fokotseha ha metabolism libakeng tse tlang pele ho cortical ( Volkow et al., 1993b; Volkow et al., 2001; Volkow et al., 2007). Ka mokhoa o ts'oanang ho batho ba kotsing e kholo ea malapa bakeng sa joala re ngotse mokhatlo pakeng tsa ho fumaneha ha D2 receptor le metabolism ea pele (Volkow et al., 2006). Botenya le bokhoba ba tahi li arolelana ka mokhoa o ts'oanang ho sitoa ho thibela boits'oaro leha ba elelloa litlamorao tse mpe. Kaha libaka tsa pele li kentsoe letsoho likarolong tse fapaneng tsa taolo ea thibelo (Dalley et al., 2004) re tiisa hore phumaneho e tlase ea D2 receptor ho striatum ea lithuto tse batenya haholo (Wang et al., 2001) le mefuteng ea litoeba tsa botenya (Hamdi et al., 1992; Huang et al., 2006; Thanos et al., 2008) e ka kenya letsoho ho nona haholo ka karolo ea DA ea ho feto-fetoha ha libaka tsa libaka tsa pele tse nkang karolo taolong ea thibelo.

Liphumano li boetse li fana ka maikutlo a hore taolo ea dopaminergic ea libaka tse tlang pele pele e le mabapi le kotsi ea botenya e ka nahanisisoa ka li-receptors tsa D2. Sena se lumellana le lithuto tsa liphatsa tsa lefutso, tse thathamisitseng mofuta oa D2 receptor gene (TAQ-IA polymorphism), e le eona e amehang khalemelong ea botenya (Fang et al., 2005; Pohjalainen et al., 1998; Bowirrat le Oscar- Berman, 2005). Ho feta moo, polymorphism ea TAQ-IA, e hlahang e baka maemo a tlase a D2 receptor bokong (striatum) (Ritchie le Noble, 2003; Pohjalainen et al., 1998; Jonsson et al., 1999) e sa tsoa fumanoa e amana le fokotseha bokhoni ba ho thibela boits'oaro bo hlahisang litlamorao tse mpe le ts'ebetso e sa sebetseng ea libaka tsa pele (Klein et al., 2007). Ka mokhoa o ts'oanang lithuto tsa preclinical li bonts'itse hore liphoofolo tse nang le maemo a tlase a D2 receptor li na le sepheo se matla ho feta li -teraka tsa tsona tse nang le litekanyetso tse phahameng tsa D2 receptor (Dalley et al., 2007). Kahoo liphumano tse tsoang thutong ea rona li fana ka bopaki bo bong ba hore mokhatlo oa li-receptor tsa D2 le taolo ea thibelo le tšusumetso e kopantsoe le karolo ea tsona ka ho feto-fetoha ha libaka tsa pele. Mabapi le taba ena hoa khahlisa ho tseba hore lithuto tsa boithuto ba kelello le tsa bongaka bo tlalehileng li fokotse taba ea bohlooho lithutong tse tlang pele ha li bapisoa le batho ba fokolang (Pannacciulli et al., 2006).

Kopano lipakeng tsa li-receptor tsa D2 le DLPFC e khahlisa haholo ho tloha ha sebaka sena se sa tsoa ameha ho thibelo ea bohato ba boomo (Brass le Haggard, 2007). Bopaki ba hore ts'ebetso ea methapo ea kutlo e etella pele tlhokomeliso ea motho ka boikemisetso ka 200-500 ms (Libet et al., 1983), e lebisitse ho ba bang ho belaella mohopolo oa "bolokolohi ba ho ikhethela" kamora liketso tsa ka boomo le ho sisinya hore taolo e bonts'a bokhoni ba ho e thibela liketso tseo re sa li batleng. Ka 'nete, ho ile ha boleloa hore matla ana a veto kapa "bolokolohi ba mahala" e ka ba tsela eo re sebelisang "bolokolohi ba ho ikhethela" (Mirabella, 2007). Tabeng ea botenya haholo motho a ka beha hore ho pepesehela lijo kapa maemo a amanang le lijo ho tla fella ka ts'ebetso e sa sebetseng ea litsamaiso tsa neuronal tse amehang ho fumaneng le ho ja lijo le hore taolo e bonts'a bokhoni ba ho thibela liketso tsena tsa boomo tsa ho batla ho ja lijo. Motho a ka nahana hore na ho se sebetse hantle joang ha DLPFC, e thusang ho thibela liketso tse hlahisang litlamorao tse mpe, joalo ka ho ja ha re lapile hobane re sa batle ho nona, ho ka fella ka ho nona. Liphumano tse entsoeng li bonts'a ho fokotseha ho hoholo hoa ts'ebetso ea DLPFC kamora ho ja lijong tse natefisang ho feta ho batho ba se nang leeme ba ts'ehetsang maikutlo ana (Le et al., 2006).

Kopano pakeng tsa ho fumaneha ha D2 receptor le medial orbitofrontal cortex (OFC) le anterior CG e tsamaisana le ho kenya letsoho ha bona ho taolo ea takatso ea lijo (Pliquett et al., 2006). Ho na le mekhoa e mengata eo motho a ka fanang ka maikutlo ka eona e sitisang ts'ebetso ea dopaminergic ea OFC le CG e ka eketsang kotsi ea ho nona.

Medial OFC e ameha ka semelo sa ho kengoa ho kenyelletsa boleng ba lijo (Roll le McCabe, 2007; Grabenhorst et al., 2007; Tremblay and Schultz, 1999) ka hona ts'ebetso ea eona ea ts'ebetso ea bobeli ho susumetso ea lijo e susumetsoang ke DA e ka baka tšusumetso e matla. ho natha lijo ka mokhoa o kopaneng oa ho sitisa. Ntle le moo, hobane ts'itiso mosebetsing oa OFC e baka ho senyeha ho khutlisetsano ea litloaelano tse ithutoang ha matlafatso a felisoa (Gallagher et al., 1999) sena se ka etsa hore o tsoele pele ho ja ha boleng ba lijo bo fokotsoa ke satiety mme o ka hlalosa Hobaneng ha tšenyo ea OFC e amahanngoa le boits'oaro bo qobelloang ho kenyeletsa ho nona (Butter et al., 1963, Johnson, 1971). Hape OFC e nka karolo ho ithuteng mekhatlo ea ntlafatso ea matlafatso le maemo (Schoenbaum et al., 1998, Hugdahl et al., 1995) ka hona e ka nka karolo ho feptjoang ke cue elicited feed (Weingarten, 1983). Sena se bohlokoa hobane likarabo tse hlahisoang ke lijo li ka ba le tlatsetso ea ho nona ho sa natsoe matšoao a tlala (Ogden le Wardle, 1990).

Dorsal CG (BA 32) e kenelletse taolong ea thibelo maemong a batlang tlhokahalo ea ho lekola ts'ebetso mme ka hona ts'ebetso ea eona e sitisitsoeng hammoho le ea DLPFC eo e sebetsanang le eona (Gehring le Knight 2000) e kanna ea senyetsa bokhoni ba motho ea nang le bothata bo feteletseng. ho thibela tloaelo ea ho ja ho feta tekano. Ventral CG (BA 25) e kenella ho arabella likarabo tsa maikutlo ho li-sisent stimuli (tse fanang ka moputso hammoho le tse feto-fetohang) (Elliott et al., 2000) le lithuto tsa ho nahana li bontšitse hore BA 25 e hlahisitsoe ke moputso oa tlhaho le oa lithethefatsi (Breiter et al., 1997, Francis et al., 1999; Berns et al., 2001). Kahoo kamano e mpe lipakeng tsa li-receptors tsa D2 le tšekamelo ea ho ja ha li pepesoa ke maikutlo a mabe ao re neng re a tlalehile ka taolo e phetseng hantle (Volkow et al., 2003) e ka kopanngoa ka phetisetso ea BA 25.

Kopano e pakeng tsa ts'ebetso ea metabolic libakeng tse tlang pele le li-receptor tsa D2 e ka bonts'a likhakanyo ho cortex ea pele ho tloha ventral le dorsal striatum (Ray le Price, 1993), e leng libaka tse amehang ho matlafatsong le sephethong sa lijo (Koob le Bloom, 1988) le / kapa ho tsoa sebakeng sa "ventral tegmental area" (VTA) le substantia nigra (SN), e leng merero ea mantlha ea DA ho striatum (Oades le Halliday, 1987). Leha ho le joalo, cortex ea pele le eona e romella likhakanyo ho striatum kahoo mokhatlo o ka bonts'a taolo ea pele ea ts'ebetso ea litaba tsa DA (Murase et al., 1993).

Ts'ebetsong ea li-non-oese tse ngata tse amanang le li-receptor tsa D2 le metabolism ea pele li ne li se bohlokoa. Ho liphumano tsa pejana re ne re bonts'itse khokahano ea bohlokoa pakeng tsa li-receptor tsa D2 le metabolism ea mantlha lithutong tse lemaletseng tse fumanehang ka D2 receptor empa li se maemong a taolo (Volkow et al., 2007)Leha ho le joalo, ho bapisoa ha khokahano lipakeng tsa botenya le lihlopha tsa taolo e ne e se ntho ea bohlokoa, ho bolelang hore ha ho na monyetla oa hore setsoalle pakeng tsa li-receptor tsa D2 le metabolism ea pele li ikhethang ka botenya (kapa tlatsetso ho latela Volkow et al., 2007). Ho ka etsahala hore litokellano tse matla ho feta tse bonoang ho batho ba batenya li bonts'a mehato e mengata ea methapo ea methapo ea D2 ka li -eseese (Bmax / Kd range 2.1-3.7) ho feta lithutong tsa taolo (Bmax / Kd range 2.7-3.8).

Ha ho toloka liphumano tsena ho bohlokoa hape ho ela hloko hore [11C] raclopride ke radiotracer eo ho tlama ho D2 receptors e amehang ho endo native DA (Volkow et al., 1994) mme ka hona phokotso ea ho fumaneha ha li-receptor tsa D2 lithutong tse batsi maemo a receptor kapa keketseho ea ho lokolloa ha DA. Boithuto bo entsoeng esale pele mefuteng ea liphoofolo tsa botona bo tlalehile phokotseho ea li-receptor tsa D2 (Thanos et al., 2008), e fanang ka maikutlo a hore phokotso ho lithutong tse feteletseng e bontša ho fokotseha hoa maemo a li-receptor tsa D2.

Correlation pakeng tsa D2R le somatosensory cortex

Re ne re se na "priori" e neng e nahana hore ho na le kamano pakeng tsa li-receptor tsa D2 le metabolism sebakeng sa somatosensory cortex. Ha e bapisoa le libaka tse ka pele kapa tsa nakoana ho na le ho fokolang ho tsejoang ka tšusumetso ea DA ho parietal cortex. Bokong ba motho, mahloriso a li-receptor tsa D2 le D2 mRNA ho parietal cortex ha e le tlase haholo ho feta libakeng tsa subcortical e lekana le e tlalehiloeng ho cortex e ka pele (Suhara et al., 1999; Mukherjee et al., 2002; Hurd et al., 2001). Le ha ho na le lingoliloeng tse lekanyelitsoeng mabapi le karolo ea "somatosensory cortex" ka ho ja lijo le botenya. Liphuputso tsa ho etsa litšoantšo li tlalehile ts'ebetso ea "cortex" ea "somatosensory" lithutong tse tloaelehileng tsa boima ka ho pepesehela litšoantšo tse bonoang tsa lijo tse tlase tsa caloric (Killgore et al., 2003) le ka satiety (Tataranni et al., 1999), mme re ne re bontšitse metabolism ea motheo e phahameng ho feta e tloaelehileng. ka cortex ea somatosensory lihloohong tse batenya (Wang et al., 2002). Hape patlisiso ea morao-rao e tlalehile hore ho batho ba batenya haholo ba nang le khaello ea leptin tsamaiso ea leptin e ile ea etsa hore 'mele oa bona o be boima le ho fokotsa ts'ebeliso ea boko bokong ba parietal ha ba ntse ba shebile tšusumetso e amanang le lijo (Baicy et al., 2007). Khokahano e sebetsang lipakeng tsa striatum le cortex ea somatosensory e sa tsoa tiisoa bakeng sa boko ba motho ka boithuto ba meta-analysis ho lithuto tse 126 tse sebetsang tsa ho nka litšoantšo, tse neng li paka tšebelisano-'moho ea cortex ea somatosensory le ea dorsal striatum (Postuma le Dagher, 2006 ). Leha ho le joalo, ho tsoa likopanong tse ithutoang re ke ke ra tseba tataiso ea mokhatlo; ka hona re ke ke ra tseba hore na botsoalle le li-receptor tsa D2 bo bonts'a ho feto-fetoha ha DA ha cortex ea somatosensory le / kapa tšusumetso ea cortex ea somatosensory ho fumanehang ha D2 receptor. Ho hlile ho na le bopaki bo bongata ba hore cortex ea somatosensory e susumetsa tšebetso ea boko ba DA ho kenyelletsa le ho lokolloa ha DA nakong ea pelehi (Huttunen et al., 2003; Rossini et al., 1995; Chen et al., 2007). Hape ho na le bopaki ba hore DA e hlophisa cortex ea somatosensory bokong ba motho (Kuo et al., 2007). Ka ha ts'usumetso ea DA e supa botsitso ebile e nolofalletsa maemo (Zink et al., 2003, Kelley, 2004), karolelano ea DA ea karabelo ea "cortex" ea lijo e kanna ea nka karolo ho theheng mokhatlo o hlophisitsoeng pakeng tsa lijo le tikoloho e amanang le lijo. lintlha le boleng bo matlafatsang ba lijo tse hlahang botenya haholo (Epstein et al., 2007).

Meeli ea ho ithuta

Taba-kholo lithutong tsena ke hore ha rea ​​ka ra fumana mehato ea methapo ea kutlo, ka hona re ke ke ra hlahloba hore na tšebetso e libakeng tse ka pele e amanang le boits'oaro ba taolo ea kelello lithutong tsena tse motenya. Le ha lithuto tsa neuropsychological mabapi le botona bo haella mme litlamorao li ferekantsoe ke mathata a bongaka a botenya (ke hore lefu la tsoekere le khatello ea mali), ho na le bopaki ba hore lithutong tse thibelang khatello ea kelello li ka sitisoa. Haholo-holo ha ho bapisoa le batho ba tloaelehileng ba boima, lithuto tse batenya haholo ha li na likhetho tse fokolang, e leng ho fumana taolo le tšitiso e thibelang le ho se sebetse hantle (Pignatti et al., 2006). Ho feta moo, litekanyetso tsa khatello ea kelello tse fokolisang khatello ea kelello (ADHD), tse kenyelletsang pherekano ho tse teng ntle le tšusumetso, li phahamisoa ho batho ba batenya haholo (Altfas, 2002). Ka mokhoa o ts'oanang ho ts'oaroa ho kopantsoe le BMI e phahameng liphoofolong tse ling (Fassino et al., 2003) le taolong e phetseng hantle BMI e boetse e amahanngoa le ts'ebetso ea mesebetsi e mengata ea ts'ebetso ea botsamaisi e kopanyang impulivity (Gunstad et al., 2007).

Hape ha re ntse re le pampiring ena re shebana le karolo eo preortalal cortex e nang le eona taolong ea thibelo le bohloka, re hlokomela hore pele-pele ho na le karolo ea ts'ebetso e mengata e fapaneng e sa qhekelloang lithutong tse batsi (Kuo et al., 2006, Wolf et al., 2007). Ho ka etsahala hore mesebetsi ea cortex ea pele-pele e kenyang botenya ke eona e amehang ho feto-fetoha ha maikutlo a DA ka litselana tsa pele tsa methapo (Robbins, 2007; Zgaljardic et al., 2006).

Ha ho ts'oaetso ea tšebetso ea pele kapa ho senyeha ha ts'ebetso ea phethahatso ha hoa totobala bakeng sa botenya. Ho hlile ho tlalehiloe ho sa tloaelehang hoa metabolism ea mantlha le ho senyeha ha tšebetso maemong a phethahatso ea mathata a fapaneng ho kenyeletsoa a nang le seabo sa dopaminergic joalo ka bokhoba ba lithethefatsi, schizophrenia, lefu la Parkinson le ADHD (Volkow et al., 1993b; Gur et al., 2000; Robbins, 2007; Zgaljardic et al., 2006).

Taba e 'ngoe hape e ne e le hore tharollo e lekanyelitsoeng ea sebaka sa PET [11C] ea mofuta oa raclopride ha e re lumelle ho lekanya ho fumaneha ha D2 receptor libakeng tse nyane tsa boko tse bohlokoa ho hokahaneng le litloaelo tse amanang le lijo tse kang hypothalamus.

Qetellong litokiso ha li bolele hore ho na le mekhatlo e kopaneng, 'me ho boetse ho hlokahala lithuto tse ling ho hlahloba litlamorao tsa ts'ebetso ea kelello ea DA ts'ebetsong ea pele lithutong tsa motenya.

Summary

Phuputso ena e bonts'a setsoalle se bohlokoa lithutong tse nyarosang pakeng tsa li-receptor tsa D2 ho striatum le tšebetso ho DLPF, medial OFC le CG (libaka tsa boko tse kentsoeng taolong ea inhibitory, tumello ea ho se sebe le ho se sebetse maikutlong le ho sitisoa ha tsona ho ka baka boitšoaro bo sa tsitsang le bo qobelloang), bo e fana ka maikutlo a hore ena e ka ba e 'ngoe ea mekhoa eo li-receptor tsa D2 tse tlase li ka sebelisang ho nona haholo ho ka nona le ho nona haholo. Ntle le moo re boetse re ngola kamano e bohlokoa pakeng tsa li-receptor tsa D2 le metabolism ho somatosensory cortex e ka fetolang thepa e matlafatsang ea lijo (Epstein et al., 2007) le e lokelang ho etsoa lipatlisiso tse ling.

lumela hore baa fokola
Re leboha David Schlyer, David Alexoff, Paul Vaska, Colleen Shea, Youwen Xu, Pauline Carter, Karen Apelskog, le Linda Thomas bakeng sa menehelo ea bona. Phuputso ena e ne e tšehelitsoe ke Lenaneo la Thupelo ea Intramural Research (NIAAA) le DOE (DE-AC01-76CH00016).

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