Cineine Cues le Dopamine ka Dorsal Striatum: Mokhoa oa ho lakatsa ho lemalla ha Cocaine (2006)

Maikutlo: Ketsahalo ea ts'ebetso ea cue e kholo joalo ka ho ts'oara koae (dorsal striatum)

  1. Christopher Wong3

+Bontša Litšebelisano

  1. 26(24): 6583-6588; doi: 10.1523/JNEUROSCI.1544-06.2006

inahaneloang

Bokhoni ba lithethefatsi tsa tlhekefetso ho eketsa dopamine ho li-nucleus li tlatsetsa tlasa litlamorao tsa bona tsa ho matlafatsa. Leha ho le joalo, lithuto tsa pele ho tsa bophelo li bontšitse hore ka ho pepesetsoa lithethefatsi khafetsa tse khothalletsoang ke lithethefatsi (boemo bo susumetsang) li qala ho eketsa dopamine ka bo bona, e leng tšusumetso e ka fokotsang boitšoaro ba ho batla lithethefatsi. Mona re lekola hore na keketseho ea dopamine e ba teng maemong a susumetsoang lithutong tsa batho ba lemaletseng koae le hore na sena se amana le litakatso tsa lithethefatsi. Re lekile lithuto tse lemaletseng koae ka koae tse leshome le metso e robeli re sebelisa positron emission tomography le [11C] raclopride (dopamine D2 receptor radioligand e amehang ka tlholisano le dopamine ea endo native). Re lekantse liphetoho dopamine ka ho bapisa tlama e tobileng ea [11C] raclopride ha lithuto li shebella video e sa nke lehlakore (litšoantšo tsa tlhaho) ha li shebella video ea cocaine-cue (lits'oants'o tsa lithuto tse tsubang koae). Tlamo e tobileng ea [11C] raclopride in dorsal (caudate and putamen) empa eseng ka har'a ventral striatum (moo li-nucleus accumbens li leng teng) e ile ea fokotsoa haholo maemong a cocaine-cue le boholo ba phokotso ena e amanang le litlaleho tsa boithati tsa ho lakatsa. Ho feta moo, lithuto tse nang le lintlha tse phahameng haholo mehatong ea matšoao a ho khaotsa le ho teba ha lithethefatsi tse bonts'itsoeng ho bolela sephetho sa kalafo, li bile le liphetoho tse kholo ka ho fetisisa dopamine ho dorsal striatum. Sena se fana ka bopaki ba hore dopamine ho dorsal striatum (tikoloho e kenelletseng thutong ea tloaelo le ts'ebetsong ea ts'ebetso) e ameha ho lakatseng mme ke karolo ea motheo ea bokhoba ba tahi. Hobane ho lakatsa ke ntho e ka sehloohong e tlatsetsang ho oeleng hape, maano a etselitsoeng ho thibela ho eketseha ha dopamine ho tsoa likarabo tse nang le maemo a mangata a ka ba molemo ho kalafo ea lithethefatsi tsa koae.

Selelekela

Lithethefatsi tsa tlhekefetso li eketsa dopamine (DA) ho li-nucleus accumbens (NAc), e leng tšusumetso eo ho lumeloang hore e ba le litlamorao tsa bona tsa ho tiisa (Di Chiara le Imperato, 1988; Koob le Bloom, 1988). Leha ho le joalo, ts'ebetso ena e matla ha e hlalose takatso e matla ea lithethefatsi le tšebeliso e qobelloang e etsahalang ha batho ba lemaletseng lithethefatsi ba pepesetsoa litloaelo tsa lithethefatsi joalo ka libaka tseo ba nkileng lithethefatsi ho tsona, batho bao tšebeliso ea lithethefatsi tsa pele li etsahetseng le paraphernalia ba neng ba tloaetse ho e sebelisa. tsamaisa lithethefatsi. Ho labalabela ho tseba lintho tse ngata ho bohlokoa molemong oa ho khutlela mokhoeng oa ho lemalla.O'Brien et al., 1998). Leha ho le joalo, kamora ho feta lilemo tse fetang tse leshome tsa ho ithuta ka litakatso tsa takatso e matla ea kelello, ts'ebetso ea eona ea methapo ea kelello e ntse e sa tsejoe (Childress et al., 2002). Hobane DA ke neurotransmitter e amehang ka moputso le ho bolela esale pele ka moputso (Bohlale le Rompre, 1989; Schultz et al., 1997), Ho lokolloa ha DA ke lithethefatsi tsa lithethefatsi ke karolo e matla ea mokhethoa oa litakatso tse kholo. Boithuto ho liphoofolo tse sebelisang maiketsetso bo ts'ehetsa maikutlo ana: ha ts'usumetso ea ho se nke lehlakore e matahantsoe le moriana o khotsofatsang, ba tla ba le bokhoni ba ho eketsa DA ho NAc le dorsal striatum (ho ba le maemo a hlakileng), 'me likarabo tsena tsa methapo ea kutlo li amahanngoa le lithethefatsi. boits'oaro ba ho sheba litoeba (Di Ciano le Everitt, 2004; Kiyatkin le Stein, 1996; Phillips le al., 2003; Vanderschuren et al., 2005; Weiss et al., 2000). Tekanyo eo maemo a hlohlelletsoang a ka lebisang ho eketseho ea DA bokong le litheko tse lumellanang tsa liphihlelo tse ikhethileng tsa litakatso tsa lithethefatsi ha li e-so ithutoe lithutong tsa batho. Mahlale a morao-rao a re nolofalletsa ho lekola hore na liphetho tse fumanoeng lithutong tsa pele ho liteko li ka fetolela boiphihlelo ba lithuto tse lemalloang ke batho ba lemaletseng lithethefatsi ha li pepesetsoa litlhare tsa lithethefatsi.

Mona re etsa lipatlisiso tsa khopolo-taba e ntseng e eketseha ho DA tlasa litakatso tsa batho ba lemaletseng lithethefatsi ha ba pepesetsoa litabatabelo tse amanang le lithethefatsi. Re ile ra nahana hore litekanyetso tsa koae li tla eketsa DA ka ntle ho maemo ha li bapisoa le keketseho ea litakatso tsa koae le hore lithuto tse nang le ts'ebeliso e matla ea litheko li ka ba le keketseho e kholo ea DA karabong ea maemo a bonolo ho feta lithuto tse nang le ts'ebeliso e mpe ea tahi. Ho leka tlhahiso-leseling ena, re ithutile lithuto tse lemalloang ke koae ea 18 ka positron emission tomography (PET) le [11C] raclopride, DA D2 receptor ligand qenehela tlholisano le endo native DA (Volkow et al., 1994). Lintho li ile tsa lekoa matsatsing a arohaneng a 2 tlasa maemo a mabeli a hanyetsanang: nakong ea tlhahiso ea video e sa nke lehlakore (pono ea tlhaho) le nakong ea tlhahiso ea video ea koae-cue (litšoantšo tse bontshang ho itukisetsa ho tsuba le ho tsuba koae ea koae)Childress et al., 1999). [11C] raclopride e tlamang e khona ho hlahisoa hape (Volkow et al., 1993), mme ho bonts'itsoe hore liphapang tsa ho tlama ka ho khetheha lipakeng tsa maemo a mabeli li bonts'a liphetoho tse tlisoang ke lithethefatsi kapa tse susumetsang boitšoaro ho DA ea kantle ho naha (Breier et al., 1997).

Lisebelisoa le mekhoa

Lintho.

Ho ile ha ithutoa lithuto tse 6 tse sebelisang lithethefatsi tse sebelisang koae tse arabileng papatsong. Lihlooho li phethile DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Khatiso ea Bone) litekanyetso tsa ts'ebeliso ea koae mme e ne e le basebelisi ba mafolofolo bonyane likhoeli tse 30 tse fetileng (mahala-free kapa crack, bonyane "ligrama tse nne" ka beke). Mekhoa ea ho qheleloa ka thoko e kenyelelitse lefu la kelello la hajoale kapa le fetileng ntle le ts'epahalo ea cocaine; nalane e fetileng kapa ea joale ea methapo ea pelo, methapo ea pelo, kapa lefu la endocrinological; nalane ea ts'oaetso ea hlooho le ho lahleheloa ke kelello> XNUMX min; le bokuli ba hajoale ba bongaka le ts'ebeliso ea lithethefatsi ntle le cocaine kapa nicotine. Lethathamo 1 e fana ka tlhaiso-leseling ea demographic le ea bongaka lithutong. Ho ile ha fumanoa tumello e ngotsoeng e fumanehang lithutong tsohle.

 

Tafole 1. 

Palo ea batho le lithuto tsa bophelo

Sekala sa boitšoaro.

Ho lekola takatso ea koae, re sebelisitse mofuta o mokhuts'oane oa Cocaine Craving Questionnaire (CCQ) (Tiffany et al., 1993), e hlahlobang takatso ea hona joale ea koae (koae ea ho sebelisa, sepheo le ho rera ho e sebelisa, tebello ea phello e ntle, tebello ea ho imoloha ho tlosoeng kapa matšoao a sithabetsang, le ho hloka taolo ea ts'ebeliso ea lithethefatsi) ka sekhahla sa pono tse ananyang tse supileng. Palo e tloaelehileng e ne e sebelisoa e le tekanyo ea takatso ea koae. CCQ e fumanoe pele le qetellong ea video.

Ho hlahloba botebo ba ho lemalla koae ka koae re sebelisitse Adiction Severity Index (ASI) (McLellan et al., 1992) le Cocaine Sele Selever Severity Assessment Scale (CSSA) (Kampman et al., 1998). ASI e lekola ho tiea libakeng tse supileng (lithethefatsi, joala, mafu a kelello, lelapa, molao, bongaka le mosebetsi) mme e fumanoe puisanong ea pele. Tekanyo e tloaelehileng ea motho ea botsang lipotso libakeng tsena tse supileng e sebelisitsoe e le mokhoa oa ho lemalla lithethefatsi. CSSA e lekanya matšoao a 18 a ts'ebeliso ea "cocaine" ea pele e lekantsoeng ka sekala sa analog ho tloha 0 ho isa 7. XNUMX. CSSA e fumanoe pele ho scan e ngoe le e ngoe.

PET scan.

Re sebelisitse qeto e phahameng + tomograph (resolution 4.5 × 4.5 × 4.5 mm ka botlalo ba halofo-halofo, siling ea 63) ka [11C] lebala la marang-rang le sebelisa mekhoa e hlalositsoeng pele (Volkow et al., 1993). Ka bokhutšoanyane, scans ea emission e ile ea qalisoa hang ka mor'a ho kenoa ka jekeng ea 4-8 mCi (ts'ebetso e ikhethileng ea 0.5-1.5 Ci / μm qetellong ea bombardment). Ho fumanoe li-scanes tse mashome a mabeli tse matla tsa matla ho tloha nakong ea ente ho fihlela 54 min. Sampling ea Arterial e ne e sebelisetsoa ho qopitsa kakaretso ea carbon-11 le e sa fetoheng [11C] moralo ka bongata ka plasma. Lintho li ile tsa hlahlojoa ka 2 ka matsatsi a fapaneng le [11C] raclopride tlasa maemo a laetsoeng ka mokhoa o sa reroang (1) ha a ntse a shebelletse video ea litšoantšo tsa tlhaho (boemo ba ho se nke lehlakore) le (2) ha a ntse a shebelletse video e bonts'ang lithuto tse tsubang koae (cocaine-cue). Livideo li qaliloe 10 min pele ho ente ea [11C] raclopride mme e ile ea ntšetsoa pele bakeng sa metsotso ea 30 ka mor'a ho enteloa ke radiotracer. Video e sa nke lehlakore e ne e na le likarolo tsa lipale tsa tlhaho tse sa hlaloseng, 'me video ea cocaine-cue e bonts'a likarolo tse senotseng tse bontšang ho reka, ho lokisa le ho tsuba koae.

Tlhahlobo ea litšoantšo.

Bakeng sa boits'oaro ba libaka, re ile ra akaretsa linako tse tsoang lipapisong tse nkiloeng 10-54 min 'me ra li sebelisa hape ka sefofaneng se kopaneng. Lifofane li ile tsa eketsoa ka lihlopha tsa tse peli ho fumana lifofane tsa 12 tse kenyang caudate, putamen, ventral striatum, le cerebellum, tse lekantsoeng ka lifofane tse 'ne, tse tharo, e le' ngoe le tse peli ka tatellano. Libaka tse ka lehlakoreng le letona li ne li kengoe. Libaka tsena li ne li reretsoe hore e fihle litekong tse matla tsa ho fumana nako ea C-11 le nako. Lisebelisoa tsena tsa nako e sebelisoang bakeng sa ho kenella linthong tsa thipa, hammoho le nako eo li-tracer tse sa fetoloang ka tsona plasma li neng li sebelisoa ho bala phetiso e sa feleng ea [11C] moralo oa leqhubu ho tloha ho plasma ho ea bokong (K1) le li-volumes tsa li -abalalisa (DVs), tse lumellanang le tekanyo e lekanang ea karo-karo ea tishu ea mahlaseli a mahlaseli a plasma, ka striatum le cerebellum, e sebelisa mokhoa oa ho hlahloba litšoantšo bakeng sa lits'ebetso tse feto-fetohang (Logan et al., 1990). Karolelano ea DV ho striatum ho eo ho eona ka cerebellum e tsamaisana le [receptor concentration (Bmax) / affity (Kd)] + 1 mme ha e nahanele liphetoho mabapi le phallo ea mali a tsoang bokong (Logan et al., 1994). Kameho ea video ea cocaine-cue ho DA e ile ea hlakoloa joalo ka phetoho ea liperesente ho Bmax / Kd mabapi le video e sa nke lehlakore.

Ho hlophisa sebaka ka har'a striatum, moo liphetoho tsa DA li etsahetseng teng re boetse re sekaseka litšoantšo tsa DV re sebelisa 'mapa oa lipalopalo (SPM) (Friston et al., 1995). E ngotsoe t Ho ile ha etsoa liteko tsa ho bapisa boemo ba ho se nke lehlakore le boemo ba cocaine-cue (p <0.05 e sa nepahala, monyako> li-voxels tse 100).

Tlhahlobo ea lipalo.

Phapang lipakeng tsa maemo a boitšoaro le litloaelo tsa PET li ile tsa hlahlojoa ka lipara t liteko (tse peli-tailing). Likahare tsa sehlahisoa li sebelisitsoe ho lekola kamano lipakeng tsa liphetoho tsa DA le mekhoa ea boits'oaro (CCQ, ASI, le CSSA).

Results

Liphello tsa likhokahano tsa koae ho [11C] mehato ea moralo

Hobane ho ne ho se na phapang lipakeng tsa libaka tse ka letsohong le letšehali le le letona, re tlaleha sephetho sa lipalo tse tloaelehileng libakeng tse ka letsohong le letšehali le tse nepahetseng. The K1 tekanyo e ne e sa fapana lipakeng tsa maemo bakeng sa efe kapa efe ea likarolo tsa mokokotlo (Lethathamo 2). Sena se bonts'a hore tlhahiso ea tracer ha e anngoe ke boemo ba koae.

 

Tafole 2. 

K1 (tsamaisa khafetsa ho tloha ho plasma ho ea ho lithane) le mehato ea DV bakeng sa maemo a sa sebetseng a video le cocaine-cue le t 'me p boleng ba papiso ea bona (lipara tse peli tse nang le mohatla t liteko)

DV e ne e le tlase haholo cue ea cocaine ho feta maemong a ho se nke lehlakore ho putamen (p <0.05) mme a bonts'a tloaelo ho caudate (p <0.06) empa ha ea ka ea fapana ka ventral striatum kapa ho cerebellum (Lethathamo 2). Tlhahlobo ea SPM e hlophisitse phokotso ea bohlokoa ea DV ho dorsal (caudate le putamen) empa eseng ho "ventral striatum"Feie. 1).

 

Setšoantšo sa 1. 

Limmapa tsa Brain tse fumanoeng le SPM li bonts'a phapang ea palo ea [thomello ea]11C] moralo lipakeng tsa boemo ba ho se nke lehlakore le maemo a koae (cocaine-cue)p <0.05, e sa nepahala, monyako> li-voxels tse 100). Hlokomela hore ho ne ho se na liphapang ho ventral striatum (plane8 canthomeatal plane).

Mehato ea Bmax / Kd, e bonts'ang D2 li-receptors tse sa luleng ke DA ea mehleng, li ne li theohile haholo cue ea cocaine ho fapana le maemo a ho se nke lehlakore ho caudate (t = 2.3; p <0.05) le ho putamen (t = 2.2; p <0.05) empa ha ea ka ea fapana ka ventral striatum (t = 0.37; p = 0.71) (Feie. 2A). Sena se supa hore cocaine e utsoellelitse ho hloekisoa ha DA ho dorsal striatum.

 

Setšoantšo sa 2. 

A, Dopamine D2 ho fumaneha ha li-receptor (Bmax / Kd) ho caudate, putamen, le ventral striatum bakeng sa maemo a ho se nke lehlakore le a cocaine-cue. B, Mehato ea ho lakatsa (e lekantsoeng le CCQ) pele (pele) le kamora (poso) tlhahiso ea livideo tse sa jeleng paate le tsa koae. C, Phallo ea Regression bakeng sa khokahano lipakeng tsa liphetoho ho DA (liphetoho liperesente ho Bmax / Kd ho tloha maemong a ho se nke lehlakore) le liphetoho litakatsong tsa cocaine (phapang ea pele le ea poso litsing tsa CCQ). Maemo a boleng a bolela ± Li-SD. Papiso e tsamaellana le paired t liteko (tse peli-tailing) *p <0.05; **p <0.01.

Litlamorao tsa likholofalo tsa koae ka ho lakatsa le ho hokahana le mekhoa ea boits'oaro

Video ea cocaine-cue e ile ea eketsa haholo litakatso tse lakatsang (CCQ) ho tloha 2.9 ± 1.4 ho isa 3.5 ± 1.4 (t = 2.9; p <0.01), athe video e sa jeleng paate ha ea ka ea e-ba joalo; lintlha pele video e ne e le 2.8 ± 1.6 mme kamora hore video e be 3.0 ± 1.7 (t = 1.1; p <0.30) (Feie. 2B). Lits'ebetso lipakeng tsa liphetoho tsa ho lakatsa le liphetoho tsa DA li ne li sa fapana bakeng sa libaka tse ka ho le letšehali le ka ho le letona ka hona re tlaleha ka likamano mabapi le mehato e tloaelehileng. Likhakanyo tsena li ne li bohlokoa ho putamen (r = 0.69; p <0.002) le ka caudate (r = 0.54; p = 0.03) empa eseng maemong a kenang ka harer = 0.36; p = 0.14) (Feie. 2C).

Tlhahlobo ea kamano lipakeng tsa liphetoho tsa DA le sekala sa kliniki e senola kamano e kholo lipakeng tsa CSSA le liphetoho tsa DA ho caudate (r = 0.55; p <0.01) le tloaelo ea putamen (r = 0.40; p = 0.10). Ka mokhoa o ts'oanang, lintlha ho ASI li ne li amana hantle le liphetoho tsa DA ho putamen e nepahetseng (r = 0.47; p <0.05), ventral striatum e ka letsohong le letšehali le le letona (r = 0.50; <0.04), le tloaelo ea caudate ea leqele (r = 0.41; p = 0.09). Ho teba ha botebo ho CSSA le ASI ho hoholo ha liphetoho tse etsoang ke DA.

Khokahano pakeng tsa mehato ea D2 ho fumaneha ha li-receptor tse fumanoeng nakong ea video e sa nke lehlakore le sekala sa kliniki (CCQ, CSSA, le ASI) li ne li se bohlokoa.

Puisano

Litlamorao tsa ho sebelisa koae ea koae ka DA ho striatum

Mona re bonts'a keketseho ho DA litabeng tsa dorsal striatum lithutong tse lemaletseng cocaine a shebelletse video e bonts'ang litheko tsa koae. Liphetho tsena li lumellana le lithuto tsa Microdialysis tse tlalehang ho eketseha ha kantle ho DA ho dorsal striatum ka litoeba tse arabang litheko tsa cocaine (Ito et al., 2002). Leha ho le joalo, lithuto tsa Microbalalysis li tlaleha keketseho ea DA ho dorsal striatum ha feela makhopho a koae a ne a hlahisoa ka phehisano (Ito et al., 2002), athe tlhahiso e sa laoleheng e eketse DA ho fapana le NAc (Neisewander et al., 1996). Thutong ea rona, litheko tsa cocaine li ne li sa laolehe hobane lithuto li ne li sa hlokoe ho hlahisa likarabo leha e le life ho shebella video, leha ho le joalo litheko tsa cocaine li hlahisitse keketseho e kholo ea DA ho dorsal striatum eseng ho "ventral striatum" (NAc e fumanehang). Sena se kanna sa bonts'a phapang lipakeng tsa parcligical le tsa bongaka paradigms; ka kotloloho, litoeba li koetliselitsoe hore ho araba litheko ho bolela ho tlisoa ha lithethefatsi, athe ba lemaletseng koae, ho pepesetsoa lits'oants'o tse "cocaine cices" ha ho bolele esale pele ho tsamaisoa ha lithethefatsi empa ho e-na le hoo ba li hlohlelletsa ho etsa boits'oaro bo hlokahalang ho fumana moriana. Ka mantsoe a mang, phepelo ea koae e ke ke ea itlhahela feela, joalo ka ha ho ka ba joalo ka tlhahiso ea phehisano ka litoeba, e hloka hore motho a fuoe boitšoaro. Kahoo, ts'ebetso ea DA ts'ebetsong ea dorsal striatum ke cocaine e bonahala e etsahala ha likarabo tsa boits'oaro li hlokahala ho fumana lithethefatsi ho fapana le litheko tsa koae tse bolelang ho tlisoa ha lithethefatsi ho sa tsotelloe karabelo e tsoang ho boitšoaroVanderschuren et al., 2005). Sena se tsamaisana le karolo ea dorsal striatum ha ho khethoa le ho qala liketso (Graybiel et al., 1994).

Dopamine ho dorsal striatum le litakatso

Thutong ena, re bonts'a kamano pakeng tsa takatso ea koae le keketseho ea DA ho dorsal striatum (caudate le putamen). Hobane monahano o ka sehloohong oa lisele tsa DA ho isa dorsal striatum o hlaha ho "antiantia nigra "Haber le Fudge, 1997), sena se tiisa tsela ea DA ea bohlasoa ea boiphihlelo boiphihlelong ba ho lakatsa. Sena se lumellana le liphuputso tse fetileng tsa monahano tse bonts'ang hore ts'ebetso ea "putamen" ho batho ba sebelisang koae ka lebaka la ts'ebeliso ea koae e ne e amana le ho lakatsa ho ts'oaroa ke koae ka ha ho hlahlojoa ke liphetoho tsa boemo ba moea (oxygen) bo itšetlehileng ka ts'ebeliso ea matla a matla a matla a matla a moea (fMRI)Breiter et al., 1997) hammoho le setsoalle se khothatsang (Risinger et al., 2005)] kapa ka tsamaiso ea methapo ea methylphenidate joalo ka ha ho hlahlojoa liphetoho tsa metabolism ea "glucose metabolism" le PET [mokhatlo o motle (Volkow et al., 1999)]. Ho lakatsa ho ts'oaroa ke khatello ea khatello ho ba hlekefetsang koae ho boetse ho amana le ts'ebetso ea dorsal striatum (ho kenyelletsa le caudate) joalo ka ha e hlahlojoa le fMRI (Sinha et al., 2005). Ka mokhoa o ts'oanang, thuto ea fMRI e neng e bapisa likarabo lipakeng tsa video e sa jeleng paate le ea koae e amanang le lets'oao le ntlafalitsoeng la BOLD ho dorsal striatum nakong ea video ea cocaine le takatso e hlahisitsoeng ke video (Garavan et al., 2000).

The dorsal striatum e ameha ka khetho le ho qala ha liketso (Graybiel et al., 1994), 'me lithuto tsa morao-rao li e tlatsetsa ho boithuto ba ho ithuta ba ho susumetsa (tloaelo), ho kenyeletsa le ho etsahalang ka tsamaiso e mpe ea lithethefatsi (Bosoeu le McDonald, 2002). Kahoo, kamano e lipakeng tsa dorsal striatal dopaminergic le cueine e susumetsang takatso ea koae e ka bonts'a mofuta oa tloaelo ea ho rata ho lemalla (ho iketsahalla)Tiffany, 1990). Boithuto bo 'maloa ba tlhahlobo ea bongaka ba bophelo ba pele le ba tleliniking bo tlalehile hore karolo ea dorsal striatum e na le monyetla oa ho pepesehela cocaine (Letchworth et al., 2001; Porrino et al., 2004; Volkow et al., 2004). Ebile, liphoofolong tsa liphoofolo tse fumanehang ka kotloloho, libaka tse sotlehileng li fetoha kahare ho koae ha koae e ntse e tsoela pele (Letchworth et al., 2001; Porrino et al., 2004). Ho joalo, ho nahanoa hore ts'ebetso ea dorsal e nka sebaka sa tlhaho sa ho qobelloa ho sebelisa lithethefatsi ho lemalletseng koae (Tiffany, 1990; Robbins le Everitt, 1999).

DA e kenya letsoho taolong ea tšusumetso le moputso (kapa ponelopele ea moputso) (Bohlale le Rompre, 1989; Schultz et al., 1997). Phuputsong ea morao-rao, ho hlahella ka video ea "cocaine" e ne e le "mophatlalatsi oa moputso" o matla (ka nalane ea boemo bo telele), empa lithuto thutong eo li ne li tseba hore moputso oa lithethefatsi (cocaine ea nnete) o ne o ke ke oa fumaneha. Mabapi le sena, liphumano tsena li tšoana le tsa lithuto tsa bophelo bo botle tse bonts'itseng likhakanyo tsa lijo tseo ba sa khoneng ho li ja, tse tlalehang DA e eketseha ka dorsal striatum e amanang le "takatso ea lijo." Le ha keketseho ea DA e ne e le nyane kamora ho pepesetsoa lijo tse khothalletsoang ho feta ka mor'a ho pepesetsoa litheko tsa koae, tataiso ea khokahano e ne e ts'oana: ha DA e eketseha le ho feta, takatso e kholo le ho feta (Volkow et al., 2002). Ho ka bonahala eka ts'ebetso ea DA ea dorsal striatum e ameha ka "takatso" (e batlang), e tla fella ka boikemisetso ba ho etsa boits'oaro bo hlokahalang ho fumana ntho eo o e batlang. Liphumano tsena li tsamaellana li fana ka maikutlo a makatsang a hore bokong ba motho, ts'ebeliso ea lithethefatsi e ka ba le ts'ebetso e ts'oanang ea maikutlo e khothalletsang boits'oaro bo hlokahalang bakeng sa ho pholoha bo bakiloeng ke litekanyetso tse nang le maemo a lijo.

Reacaction of the striatum le ho lemalla ho lemalla

Liphetoho tse senotsoeng tsa DA li ne li boetse li amahanngoa le likhakanyo tsa bokhoba ba tahi (bo lekantsoeng le ASI le CSSA); Ha bophahamo ba bokhoba ba lithethefatsi bo le matla, e eketseha leholo la DA. Hobane dorsal striatum e bohlokoa mokhoeng oa ho ithuta tloaelo, mokhatlo ona o ka bonts'a ho matlafatsa ha litloaelo ha tsoelo-pele e ntse e tsoela pele. Hobane CSSA ke tekanyo e bonts'itsoeng ho bolela sephetho sa kalafo lithutong tse lemaletseng koae.Kampman et al., 2002), sena se fana ka maikutlo a hore ho busetsoa hoa sistimi ea DA ho litheko tsa lithethefatsi e ka ba sehlahisoa sa litholoana tse mpe lithutong tse lemaletseng koae. E boetse e fana ka maikutlo a hore likhathatso tsa mantlha tsa ts'ebetso ea ts'oaetso litabeng tsa bokhoba ke likarabo tsa maemo a amanang le ts'ebetso tse lebisang ts'ebetsong ea litsela tsa DA tse tsosang litloaelo tsa boits'oaro tse lebisang ho batleng lithethefatsi le ts'ebeliso e mpe. Ho ka etsahala hore likarabo tsena tse nang le maemo a methapo ea kutlo li bonts'a liphetoho tsa corticostriatal le corticomesencephalic glutamatergic (Kalivas le Volkow, 2005).

Li-bokella le ho lakatsa

Phuputso ena ha e fumane kamano pakeng tsa ho lakatsa le liphetoho tsa DA ho ventral striatum (moo NAc e leng teng). Sena e ne e le se sa lebelloang hobane liphuputso tse entsoeng ka liphoofolo tsa mahlale li bonts'itse hore NAc ke karolo ea lipakeng tsa "neural circry" tse arolelanang kholofalo ea cueine e kenyellelitseng ho ts'oeleng koae ea koae (Fuchs et al., 2004). Sena se ka fana ka maikutlo a hore ho kenya letsoho ha NAc ho lakatseng ke nondopaminergic. Ka 'nete, likhakanyo tsa glutamatergic ho NAc li bile le tšusumetso ka kotloloho mekhoeng e amanang le lithethefatsi e amanang le cue, e leng tšusumetso e sa thibeloang ke bahanyetsi ba DA (Di Ciano le Everitt, 2004). Leha ho le joalo, bafuputsi ba bang (Gratton le Wise, 1994; Kiyatkin le Stein, 1996; Duvauchelle et al., 2000; Ito et al., 2000; Weiss et al., 2000), leha e se kaofela (Brown le Fibiger, 1992; Bradberry et al., 2000), li bonts'itse keketseho ea DA ho NAc ka tlhahiso ea litlolo tsa koae. Joalokaha ho hlalositsoe, sena se ka bonts'a maemo a tlisoang ke litšupiso tlas'a (contingent vs noncontingent). Hape, sepheo sa lithuto tsa pele li sebeletsa mosebetsi o fapaneng le oa lithutong tsa morao-rao; hobane ba supa ho fumaneha ha koae, ba sebetsa e le tšusumetso ea khethollo, athe haeba e pentiloe kapa e amana le tlhahiso ea koae (joalo ka litloaelo li le teng thutong ea hona joale), li na le tšusumetso. Leha ho le joalo, li ka bonts'a phapang ea mefuta (batho khahlanong le litoeba), liteko tsa liteko (livideo tse bonts'ang li-cv vs ho ba teng hoa li-cue), le mekhoa ea ho lekanya DA (PET vs microdialysis le voltammetry).

Meeli ea ho ithuta

Phapang e fokolang ea sebaka sa marang-rang ea PET e re qobelletse ho lekanya striatum ea ventral ho fapana le NAc. Hape, tharollo ea eona ea nakoana e fokolang ea nakoana e re lumelletse ho bona liphetoho tsa DA ka nako ea metsotso ea 20-30, ho fokotsa bokhoni ba rona ba ho fumana keketseho ea DA ea nako e khuts'oane joalo ka ha ho tlalehiloe molemong oa cocaine ka voltammetry (Phillips le al., 2003). Ntle le moo, [11C] raclopride mokhoa o loketse haholo ho fumana tokollo ea DA libakeng tse phahameng tsa D2 segokanyipalo sa receptor joalo ka striatum, empa eseng maemo a tlase a receptor joalo ka libaka tse extxpriatal, tse ka hlalosang hore na hobaneng ha re sa bonts'a liphetoho tsa DA ho amygdala, moo lithuto tsa liphoofolo li bonts'itseng likhahla tsa DA tse nang le cue-elicited (Weiss et al., 2000).

Leha re bonts'a hore phapang ea boholo ba DA e bakoang ke cocaine cue e amana le ho teba ha ts'ebetso ea ho lemalla, e kanna ea supa phapano ea ho nchafatsoa hoa lisele tsa DA tse ka bang pele ho tlhekefetso ea lintho. Thutong ena, 17 ea lithuto tsa 18 e ne e le banna mme ka hona lithuto tse tlang li hlokahala ho hlahloba phapang ea bong.

Nahanisisa

Hobane DA e nyoloha dorsal striatum e hlahisitsoeng ke lithahasello tsa lithethefatsi, sena se fana ka bopaki ba karolo ea bohlokoa ea tsela ea mantlha ea DA ho lakatsa le ho lemalla lithethefatsi tsa koae. E boetse e fana ka maikutlo a hore likhakanyo tse ka thibelang ho eketseha ha litheko tsa DA e tla ba lipheo tse hlakileng tsa nts'etsopele ea lipallo tsa meriana ho phekola lekhoba la koae.

Tlhokomeliso e kenyellelitsoe ho bopaki.

Liphetho tse tšoanang tsa keketseho ea dopamine ho dorsal striatum nakong ea litakatso tsa koae li tlalehiloe e le data ea pele ho Wong et al. (2003).

Mongolo o botlaaseng ba leqephe

  • E amohetse April 10, 2006.
  • Phetolelo e amohetse May 8, 2006.
  • E amohetse May 14, 2006.

  • Mosebetsi ona o tšehelitsoe ke National Institutes of Health Intramural Research Program (National Institute on Alcohol Abuse and Alcoholism), ke Lefapha la Energy ofant Grant DE-AC01-76CH00016, le National Institute on Drug Abuse Grant DA06278-15. Re leboha David Schlyer, David Alexoff, Paul Vaska, Colleen Shea, Youwen Xu, Pauline Carter, Kith Pradhan, Karen Apelskog, Cheryl Kassed le Jim Swanson ka menehelo ea bona.

  • Litaba li lokela ho lebisoa ho Dr. Nora D Volkow, Setsi sa Naha sa Tlhekefetso ea Lithethefatsi, 6001 Executive Boulevard, Kamore ea 5274, Bethesda, MD 20892. Email: [imeile e sirelelitsoe]

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