Ho ithuta hantle ka botho bo batlang bocha le li-dopamine auto-receptors. Li-auto-receptors li thusa ho laola boholo ba dopamine e lokolotsoeng. Maemo a tlase a li-auto-receptors a bolela hore dopamine e ngata e lokolloa bakeng sa ts'usumetso e itseng. Dopamine e phahameng e etsa hore na rialo * eng kapa eng * e be e thabisang, kapa e susumetsang potolohong ea moputso.
Ho fumaneha ha Midbrain Dopamine Receptor Ho Kopantsoe le Mekhoa e Meholo ea ho Batla Batho ba Thato ho Batho David H. Zald, 1,2 Ronald L. Cowan, 2,3 Patrizia Riccardi, 4 Ronald M. Baldwin, 3 M. Sib Ansari, 3 Rui Li, 3 Evan S. Shelby, 1 Clarence E. Smith, 3 Maureen McHugo, 1 le Robert M. Kessler3 The Journal of Neuroscience, December 31, 2008, 28 (53): 14372-14378; Doi: 10.1523 / JNEUROSCI.2423-08.2008 Mafapha a 1Psychology, 2Psychiatry, le 3Radiological Science, Univesithi ea Vanderbilt Nashville, Tennessee 37240, le 4Department of Nuclear Medicine, Albert EinsteXx, New York Brinxx.
inahaneloang
Litšobotsi tsa botho bo batlang menahano ke ntho e ka sehloohong e ka bakang tlhekefetso ea ts'ebeliso e mpe ea lithethefatsi le boits'oaro bo bong bo sa bolokehang. Mefuta ea khalefo ea Rodent e bonts'a hore ho arabela ka boiphihlelo bo phahameng ho amana le taolo e fokotsang ea inhibitory autoreceptor ea li-neuron tsa midbrain dopamine. Ho nahanoa hore liphapang tse sebetsanang le tšebetso ea dopamine le tsona li ipapisitse le botho ba ho batla lintho tse ncha ho batho. Leha ho le joalo, liphapang tse ka hara sisteme ea dopamine ea litoeba le batho, le mekhoa ea ho lekola mefuta e arabileng ea ho araba / ho batla mefuta eohle e siea ho sa hlaka hore na mehlala ea liphoofolo e re thusa joang ho utloisisa botho ba motho. Phuputsong e teng hona joale re ile ra hlahloba kamano lipakeng tsa mekhoa e meng e batlang e sa tloaelehang ho batho le D2-like (D2 / D3) phumaneho ya ho amohela se fumanehang sebakeng sa substantia nigra / ventral tegmental.
Ho ipapisitsoe le lingoliloeng tse sebelisitsoeng nakong e fetileng re boletse hore ho batla lintho tse ncha ho tla tšoauoa ka ho fokotsoa ha li-receptor tsa D2-auto (auto). Batho ba baholo ba mashome a mararo a metso e mene ba phetseng hantle (banna ba 18, basali ba 16) ba phethetse Scidimensional Personality Questionnaire-Novelty-Searching Scale le ho hlahlojoa ha PET ka D2 / D3 ligand [18F] fallypride. Litšobotsi tsa botho bo Batlang Novelty li ne li amahanngoa hampe le ho fumaneha ha li-receptor tse kang D2 sebakeng sa "ventral midbrain", e leng tšusumetso e ileng ea lula e bohlokoa kamora ho laola lilemo. Re hakanya hore ho fumaneha ka mokhoa o tlase oa "midbrain" (auto) receptor e bonoang ho batho ba batlang lipalesa tse phahameng ho lebisa ho likarabo tse tlotlisitsoeng tsa dopaminergic ho litaba tse ncha le maemo a mang a khothalletsang tokollo ea dopamine.
Mantsoe a bohlokoa: autoreceptor; dopamine; D2; sebaka sa ho arohana ha methapo ea methapo, substantia nigra; maikutlo; tšusumetso; moputso; botho
Selelekela
Tšobotsi ea botho ea ho batla bocha e fana ka maikutlo a hore na motho o arabela joang ha a susumetsoa ke lipale kapa maemo a etsang lintho tse hlalosang le thabo e ntle (Cloninger, 1986). Tšobotsi ke e 'ngoe ea liphatlalatso tse ntle tsa tšebeliso ea lithethefatsi le boits'oaro bo bong bo kotsi (Howard et al., 1997). Lithuto tsa Rodent li fana ka mokhoa o ts'oanang le oa batho ba batlang bocha, hobane litoeba tse bonts'ang karabelo tse phahameng tsa makoloi ho tikoloho e ncha li kotsing ea ho itlhomella ka tsamaiso ea psychostimulants (Piazza et al., 1989).
Lithuto tsa Neuropharmacological li bonts'a hore litoeba tse phahameng tse arabelang tse ngata li na le litheko tse phahameng tsa basal le li-extracellular dopamine (DA) ka har'a li-bokellase tsa nucleus ha li bapisoa le ba arabetseng ba sa tsebeng ho ngola (Bradberry et al., 1991; Piazza et al., 1991a; Hooks et al., 1992) . Ho lokolloa hona ha DA ho bonahala ho bonahala e le sesosa sa taolo e fokolisitsoeng ea taolo ea methapo ea mokokotlo ea DA e hlahisang li-neurons, ka hore litheko tse phahameng tsa ho araba li bontša ho fokotsoa ha D2 receptor-indedu (ho nahanoa hore autoreceptor mediated) thibelo ea ho thunya ha DA (Marinelli le White, 2000) .
Ka har'a midbrain ea DA, somatodendritic D2-like autoreceptors e fana ka melaoana ea thibelo ea khatello ea methapo ea DA (Aghajanian le Bunney, 1977; White and Wang, 1984; Lacey et al., 1987; Mercuri et al., 1992). Somatodendritic autoreceptors e susumetsa tokollo ea lehae ea somatodendritic ea DA hammoho le ho lokolloa ha DA ho tsoa libakeng tsa terme tsa axon, ka matla a lekanang a litlamorao tsena ho fapana ho latela sehlopha sa DA sa cell le sebaka sa terminal (Maidment le Marsden, 1985; Westerink et al., 1996 ; Cragg le Greenfield, 1997; Chen le Pan, 2000; Adell le Artigas, 2004). Li-receptor tsa nakoana tsa D2 ke li-subtype tse ngata haholo tse fumanehang ka ho fetisisa ho midbrain (Sesack et al., 1994; Khan et al., 1998), hape li fana ka thibelo e matla ea tokollo ea DA (Mercuri et al., 1997). Li-receptors tsa Somatodendritic D3 (Diaz et al., 2000) le tsona li hlokometsoe ho bapala ts'ebetso ea autoreceptor (Levant, 1997; Tepper et al., 1997), empa ha e ngata haholo (Tepper et al., 1997; Gurevich le Joyce, 1999 ) le ho fana ka tšusumetso e laoloang ke melao ho feta D2 autoreceptors (Millan et al., 2000; Sokoloff et al., 2006). Karolo e nyane ea li-receptor tse kang D2 tse tšoanang le tsona li tloaetse ho kenya litlatsetso tsa glutamatergic ho li-neuron tsa DA (Pickel et al., 2002), e fana ka tsela e eketsehileng eo li-receptors tsa midbrain D2-like receptors li ka sebelisang tokiso ea thibelo ea lisele tsa DA (Koga le Momiyama, 2000) .
Ho nahanoa hore liphapang tsa motho ka mong tšebetsong ea DA le tsona li ka baka tšobotsi ea batho ba batlang bocha ho batho (Dellu et al., 1996). Leha ho le joalo, ho na le liphapang tse kholo tsamaisong ea DA ea litoeba le batho (Berger et al., 1991; Frankle et al., 2006). Ntle le moo, ha ho hlake hore na mefuta ea liphoofolo e hlahlobang likarabo ho e ke keng ea qojoa e na le tšibollo ea ho itlhahisa ho batho e sa reng letho. Ho tseba bokhoni ba ho fetolela ba mefuta ea liphoofolo ho tsebisa likarolo tse ka tlase tsa sebopeho sa motho, re lekotse hore na ho se tšoane hoa litaba tse fumanehang ho amanang le litaba tse ncha ho amana le D2-like binding (BPND; index ea ho se fumanehe habonolo ea receptor) bohareng ba mpa. batho ba phetseng hantle. Kaha re na le BPND e kang D2 joalo ka bohareng ba mpa e bonahatsa taolo ea autoreceptor ea li-neuron tsa DA, re boletse hore mekhoa e meng e batlang bocha e tla amana ka ho felletseng le BPND e kang BPND bohareng ba mpa.
Lisebelisoa le mekhoa
Barupeluoa. Barupeluoa ba mashome a mararo a metso e mene ba nang le letsoho le letona ba phetseng hantle (ba bolelang lilemo = 23.4, li-18-38; banna ba 18, basali ba 16) ba qetile thuto. Barupeluoa bohle ba fane ka tumello e ngotsoeng e nang le tsebo e amohetsoeng ke Boto ea Thupelo ea Setsi sa Univesithi ea Vanderbilt. Pele ho amoheloa mohatong oa PET oa thupelo, bankakarolo bohle ba ile ba fuoa tlhahlobo ea 'mele bakeng sa ho lekola litšitiso bakeng sa ho nka karolo ha thuto. Bafetoleli ba phethile tlhahlobo ea mafu a kelello (Puisano le Clinical Clinical bakeng sa DSM-IV) (E etellang pele., 1997) ho hlahisa pale ea kelello ea kelello ea Axis I. Barupeluoa le bona ba ne ba qheletsoe ka thoko haeba ba ne ba nkile li-psychostimulants makhetlo a fetang a mabeli. Barupeluoa le bona ba ne ba sa qheleloe kathoko haeba ba ne ba ka fihlela mokhoa oa ho its'epa nicotine, kapa ba tsubang letsatsi le leng le le leng.
Tekanyo ea ho Batla Tsebo. Barupeluoa bohle ba phethile Sekala se Batlang ho Bua ho tsoa ho Tridimensional Personality Questionnaire (Cloninger, 1987a). Cloninger o ile a nts'etsapele Novelty-Seeking Scale ho lekola "tšekamelo ea ho itlhabisa ka matla kapa ho hlasimoloha ka lebaka la tšusumetso e ncha kapa litlhahiso bakeng sa meputso e ka bang teng kapa tokollo e ka bang teng ea kotlo, e lebisang ho ts'ebetsong khafetsa ea ho lekola meputso e ka bang teng le ho ba mafolofolo ho qoba boithati le kotlo e ka bang teng ”(Cloninger, 1987b). Sekala sena se na le lipotso tse 34 tsa 'nete tse fosahetseng, tse ajoang ka lihlapiso tse' ne: NS1: ho nyakalla ha ho hlahloba (vs rigidity stoic), e tlisang khetho le karabelo nthong e ncha; NS2: ho potlaka (vs ho bonahatsa), ho amang lebelo la ho etsa liqeto; NS3: extravagance (vs reservation), e khahlisang batho ba ikemiselitseng ho sebelisa chelete ka bolokolohi; le NS4: ho hloka taolo (vs regimentation), ho amang motho hore o itlela feela ebile ha a thibeloe ke melao le melaoana. Lenane la lipotso le fumanoe e le hore lintlha tse phahameng li bonts'a ho batla ho ncha.
Ho lekola ha litšoantšo ka leihlo la boqhetseke. Magnetic resonance imaging (MRI) scans of the brain were used using nyembamba dikarolo inversion tse lokiselitsoeng T1-boima bo senyehileng gradient a hopotse tatellano [IR SPGR, nako ea echo (TE) = 3.6, nako ea ho pheta-pheta (TR) = 19, TI = 400, 24 cm tšimo ea pono] lifofaneng tsa sagittal (bophara ba 1.2 mm) le boea ba coronal (slice thick 1.4 mm). Ntle le moo, ho ile ha fumanoa li-slices tse potlakileng tsa echo axial spin density boima (TE = 19, TR = 5000, 3 mm) le T2-weighted (TE = 106, TR = 5000, 3 mm thick) ho netefatsa hore barupeluoa ha ba na tlhekefetso efe kapa efe ya sebopeho.
Tlhatlhobo ea Positron emission tomography. Ho fumaneha ha receptor e tšoanang le D2 ho ne ho lekantsoe le positron emission tomography (PET) le kamano e phahameng ea D2 / D3 radioligand [18F] fallypride. Litšoantšo tsa PET li phethetsoe ho skena sa GE Discovery LS PET (General Electric). Lihlooho li ne li behiloe ho skena ho lumella pokello ea selae sa axial se ts'oanang le sefofane sa orbitomedial se nang le bohale bo phahameng ba cingate le likarolo tse tlase tsa nakoana nakong ea pono. [18F] Fallypride (5 mCi, ketso e ikhethileng> 2000 Ci / mmol) e ile ea entoa nako e fetang ea 30 ka catheter e lulang. Lisebelisoa tsa serial tsa nako e ntseng li eketseha li entsoe nakong ea hora ea pele kamora ente ea radiotracer. Kamora khefu ea metsotso e 15-20, ho ile ha bokelloa lisene tsa bobeli ho feta metsotso e 50 e latelang. Ho ile ha fanoa ka khefu ea bobeli ea metsotso e 20-30, e lateloe ke seteishene sa boraro sa litekanyetso tse nkang 50 min. Nako e atolositsoeng ea ho lekola e lumelletsoeng bakeng sa mofuta o tsitsitseng oa kinetic e lekana ka bobeli libakeng tsa bokantle le tsa pelehi. Khalemelo e lekantsoeng ea "attenuation" e entsoe ho sebelisoa melamu e potolohang ea 68G / 68Ga pele ho sekeni ka seng.
Sekenara sa GE Discovery LS se sebelisitsoeng thutong ena se na le axial resolution ea 4 mm le ka qeto ea sefofane ea 4.5-5.5 mm ka botlalo-half-maximum (FWHM) bohareng ba lebala la pono. Qeto ena e lumella ho bonoa ha [18F] fallypride BPND sebakeng sa substantia nigra (SN) / ventral tegmental (VTA) [bona Kessler et al. (1984), bakeng sa puisano ea litlhoko tsa tharollo ea sebaka sa ho sibolla tšebetso ho SN]. Setšoantšo sa 1 se bonts'a mohlala oa ho ts'oaroa ha midbrain D2-joalo ka ho kenya letsoho ho morupeluoa a le mong. Ho bohle ba nkang karolo, litlhōrō tsa [18F] fallypride BPND li ka bonoa ho SN. Leha ho le joalo, FWHM ha e fane ka bokhoni ba ho khetholla ka ho hlaka lipakeng tsa batho ba fapaneng ba lisele tsa DA, e thibela ho phatlalatsoa ka mokhoa o hlakileng oa VTA ho SN e haufi, e nang le li-receptor tse phahameng tsa D2-like. Lithuto tse fetileng li bonts'itse ts'ebetso e ntle ea ho kenella le ho ts'epahala ho latela tekanyo ea [18F] fallypride BPND bakeng sa DA midbrain ho qeto ea scanner (Mukherjee et al., 2002; Riccardi et al., 2006). [18F] fallypride e tlama le kamano e phahameng ho li-presynaptic le li-postynaptic D2-receptors (Mukherjee et al., 1999). Leha ho le joalo, hobane polelo ea receptor ea DA ka har'a midbrain e laoloa ke D2-short receptor subtype (Khan et al., 1998), phapang ho [18F] fallypride BP kahare ho mpa e nkoa e tsamaisoa ke liphapang tsa motho ka mong ho D2-khutšoanyane autoreceptors.
Setšoantšo sa 1. [18F] Fallypride BPND e bohareng ba DA ba taba ka bomong. A, Litlhoro tse peli (tse tšoailoeng ka metsu) li tsamaellana le SN. Methati e phahameng ea BPND e ka bonoa hape ho lobe ea nakoana ea nakoana, le mokokotlong oa basal. B, Ho phatloha ha sebaka sa midbrain sa DA thutong e le 'ngoe. Methati ea bohlokoa ea BPND le eona e ka bonoa ka har'a coliculus e ka tlase ho setšoantšo. Sekala sa 'mala se tloha bopherese (tlase: BPND 0.50), ho ea bosehla (holimo: BPND> 4.0).
Tlhahlobo ea data. Ho fokotsa liphoso tse ka bang teng ka lebaka la ho sisinyeha ha hlooho, li-scan tsa PET tsa serial li ile tsa ngolisoa ka mokhoa o sebelisanang le algorithm ea 'mele (Wells et al., 1996; Maes et al., 1997). Litšoantšo tsa parameter tsa BPND li baliloe ho sebelisoa mokhoa o felletseng oa sebaka sa litšupiso (Lammertsma et al., 1996) le cerebellum e sebetsang e le sebaka sa litšupiso. Le ha cerebellum e na le maemo a tlase a li-receptor tsa D2 (Hurley et al., 2003), ha li na tšusumetso e nyane likhakanyong tsa [18F] fallypride BPND (Kessler et al., 2000). Habohlokoa le ho feta, ngollano lipakeng tsa likhakanyo tsa BPND tse tsoang sebakeng sa litšupiso tsa cerebellar le meralo ea Logan (ho sebelisoa ts'ebetso ea ho kenya letsoho ea plasma) e bontša khokahano e phahameng haholo (r> 0.99) libakeng tse ngata tsa boko (Kessler et al., 2000), e bontšang hore ts'ebeliso ea sebaka sa litšupiso sa cerebellar ha e hlahise phoso efe kapa efe ea bohlokoa maemong a amanang le BPND a libaka tse fapaneng tsa boko.
Setšoantšo sa BPND se seng le se seng sa morupeluoa se ne se hokahantsoe le MRI ea bona e boima ba T1 e ipapisitse le palo ea mantlha ea boima bo lekantsoeng ba litekanyo tse matla tsa PET ho MRI e sebelisang tlhaiso-leseling e tiileng ea 'mele (Wells et al., 1996; Maes et al., 1997 ), Setšoantšo ka seng sa sebopeho sa MRI le BPND se ne se kentsoe sebakeng se tloaelehileng sa stereotactic ho ipapisitsoe le 'mele o seng thata oa' mele oa setšoantšo sa PET / MRI se entsoeng ka setšoantšo sa PET / MRI (Rohde et al., 2003). Ho tseba katleho ea ngoliso ea mantlha ea "midbrain", ka letsoho re ile ra ngola matšoao a 'maloa ho potoloha midbrain, ho kenyeletsoa le bohale bo kamorao ho le letona le le letšehali la "colliculus" e ka pele, boholo ba ntlha e ka ho le letona le le letšehali la cerebral peduncle le fossa e kenelletseng ho z = -10, le ntlha e tlase-tlase ea ts'ebetso ea supramammillary. Har'a lithuto tse 34, 33 e bonts'itse bokhabane bo bohareng ba bohareng ba 'mele, ho se na tag e fapaneng ka> 2 mm ntlheng efe kapa efe ho tsoa ho khokahanyo ea tag (ho tsena lithuto tse 33, sebaka se bolelele ho tloha ntlheng e ngoe le e ngoe ho tloha ho tag e tloaelehileng e ne e le <1 mm bakeng sa mongolo o mong le o mong o hlahlojoa). Ha ho fanoa ka tharollo ea sebaka sa litšoantšo tsa PET, tekanyo ena ea ngoliso e fosahetseng e maemong a subvoxel, mme e tla ba le tšusumetso e nyane liphethong. Morupeluoa oa ho qetela o bonts'itse bopaki bo boholo ba ho ngolisoa hampe, haholoholo ho latela li-tag tsa colliculus. Re lekile ho lokisa sena re sebelisa lenaneo la FSL-FLIRT (Jenkinson et al. 2002) ka boima bo behiloeng masekeng ea midbrain, empa sets'oants'o se ngolisitsoeng se ntse se bonts'a bopaki ba ngoliso e fosahetseng. Ka ha ngoliso e tobileng e ikhethileng bokong ba boko e ke ke ea lokisa litaba tsa tokiso, re qhelelletse ka thoko taba ena tlhahlobisong ea hoqetela. Litlhahlobo tsohle tsa mantlha ka hona li tlalehiloe ho ipapisitsoe le bankakarolo ba 33, leha liphetho tsohle tse tlalehiloeng li ile tsa lula li le bohlokoa ha morupeluoa enoa a kenyelelitsoe.
Bobeli bo bonolo (motsotso oa sehlahisoa sa Pearson) le likamano tse sa lekanyetsoang li ne li baloa ka boikemelo bakeng sa voxel e ngoe le e ngoe ea litšoantšo tse tloaelehileng tsa BPND tse sebelisang software e tloahelehileng e sebelisitseng litlhahlobo ho latela mekhoa e fanoeng ke Zar (1999). Hobane litšoantšo tsa BPND li boreleli ka tlhaho ha li bapisoa le boholo ba sebopeho sa thahasello, ha ho na tlhotlo e eketsehileng ea sebaka e ileng ea etsoa pele e hlahlojoa. Boholo ba lihlopha li ile tsa baloa e le li-voxels tsohle tse kopaneng tse fetang moeli o moholo oa p <0.05 (e sa nepisoang). Bakeng sa sebaka sa midbrain sa DA, re hloka moeli oa li-voxels tse 15. Moeli ona o ne o ipapisitse le boholo bo lekantsoeng ba FWHM (ho tloha masaleng a litšoantšo tsa BPND) kahare ho sebaka sa midbrain sa DA, le sebaka sa lipatlisiso sa 30 x 18 x 14 mm (sebaka sa lipatlisiso se latetse mela ea midbrain). Boholo ba li-voxels tse 15 bo fihlela sekhahla sa bohlokoa ba sehlopha sa p <0.05 joalo ka ha e baloa ke ketsiso ea Monte Carlo (liphetolelo tse 1000) ho sebelisoa AlphaSim (http://afni.nimh.nih.gov/pub/dist/doc/manual/AlphaSim .pdf). Bakeng sa tlhahlobo ea tlhahlobo ea karolo e setseng ea boko, ho ne ho hlokahala moeli oa li-voxels tse 72 molemong oa bohlokoa, ho ipapisitsoe le lipalo tsa AlphaSim le p = 0.05, moelelo oa FWHM bokong bohle le ho kenyelletsoa ha li-voxels tsohle tse nang le BPND 0.40 e bolelang. Liphuputso tse hlahlobang likamano tsa voxelwise lipakeng tsa litšobotsi tsa botho le tlhaiso-leseling e nepahetseng li tlameha ho lokisa ho sebetsana le bothata ba lipapiso tse ngata. Joalokaha ho hlalositsoe kaholimo, bakeng sa litlhahlobo tsa rona tsa mantlha re totobalitse tekanyetso ea sebaka sa ho fokotsa likotsi tsa litholoana tse ntle tsa bohata. Mokhoa ona o lumella bonolo mabapi le boholo ba litlamorao (bo tsamaellanang le boholo ba likamano tse itekanetseng le bo itekanetseng lipakeng tsa sekala sa botho le mehato e meng), empa e lekanyetsa bokhoni ba ho bona mekhatlo e nyane ea molumo. Mokhoa o mong oa ho lokisa lipapiso tse ngata ke ho fetola boleng ba p bo amanang le boholo ba sephetho. Ho fumana boleng ba p bo lokisitsoeng, re fetotse boleng ba r ho ba lintlha tsa Z, mme ra beha maemo a bohlokoa re sebelisa sengoloa sa ptoz ho FSL (Smith et al. 2004) kamora ho bona hore sebaka sa lipatlisiso sa midbrain se na le likarolo tse 23 tsa tharollo. Ntle le moo ho boletsoeng ka kotloloho, ho tlalehiloe boleng ba boleng bo sa nepahalang.
Results
Tlhahlobo ea khokahano ea Voxelwise e senotse kamano e kholo e fapaneng lipakeng tsa Total Novelty-Seeking Scores le [18F] fallypride BPND ho DA midbrain bilallyally (palo e felletseng = li-voxels tse 89, khokahano e mahareng ea sehlopha kaofela, r = -0.44, p <0.01). Tlhora e shebaneng le tlholisano e fumanehang sebakeng se nepahetseng sa SN / VTA se Talairach e hokahanya x = 4.5, y = -22, z = -14.5, r = -0.68, p <0.00005 (Setšoantšo sa 2), ka tlhoro e nyane e hlahang ho ka ho le letšehali SN (x = -13, y = -25, z = -11 r = -0.53, p <0.005). Hobane maemo ka bobeli a li-receptor tsa DA le mekhoa e metle ea ho batla lintho tse ncha e fokotseha ka lilemo, re entse tlhahlobo ea likamano e laolang lilemo. Ho laola lilemo ho bile le phello e nyane liphethong (palo yohle = li-voxels tse 71, khokahano e akaretsang ea sehlopha kaofela, r = -0.43, p <0.05). Likhokahano tsa tlhoro li hlahile ka likhokahanyo tse ts'oanang, 'me tsa lula li le bohlokoa haholo (ka ho le letona, r = -0.64, p = 0.0001, left r = -0.51, p <0.005). Haeba ho sebelisoa mekhoa e thata haholo ea boholo ba phello, ka litheko tsa p tse lokisitsoeng bakeng sa palo ea likarolo tsa tharollo sebakeng sa lipatlisiso, tsepamiso ea tlhoro ea SN / VTA e lula e le bohlokoa tlhahlobisong ea mantlha (p (khalemeloa) <0.005) le data e khalemetsoeng ka lilemo (p (khalemeloa) <0.01), ha SN / VTA ea leqeleng e bonts'a tloaelo ea bohlokoa ea lipalo.
Setšoantšo sa 2. Khokahano e fapakaneng lipakeng tsa [18F] fallypride BPND ho DA midbrain le lintlha tse felletseng tsa Novelty-Search. A e bontša selae sagittal ka SN e nepahetseng. B e fana ka morero oa ho hasanya karolo ea Kakaretso ea karolo e 'ngoe le e' ngoe ea bankakarolo le [18F] fallypride BPND tlhophisong ea tlhoro. C e bonts'a letoto la likhae tsa axial ka har'a midbrain ho tloha ho az ea -10 ho isa ho -19. Ho A le C, limmapa tsa parametric li ne li thibetsoe ho bonts'a li-voxels tse nang le likhokahano tse fetang p <0.05 level (e sa lokisoang) bakeng sa boholo, ka libaka tse khubelu tse fetang r = -0.50. R, Ka ho le letona; L, ka ho le letšehali.
Re boetse ra lekola hore na bong bo susumelitse botsoalle lipakeng tsa DA midbrain BPND le mokhoa o mocha oa ho batla (joalo ka ha ho lekantsoe ke tšebelisano lipakeng tsa bong le midbrain BPND ka ho noha lintlha tse ncha). Litlhahlobo tsena li bonts'itse hore ho ne ho se na tšusumetso ea bong kamanong e teng lipakeng tsa ho batla ho ncha le midbrain BPND. Mokhoa oa likamano o hlahileng ho tsoa tlhahlobisong ea Kakaretso ea ho Batla Tlhaho o ne o totobetse ebile o ne o sa bontše sebopeho sa lefats'e sa maemo a theotsoeng a li-receptor tse kang tsa D2 bokong. Ha ho na libaka tse ling tsa boko tse bonts'itseng likamano tsa boholo kapa boholo ba midbrain. Ho joalo, ke libaka tse ling tse tharo feela tsa boko tse fihletseng sekoaelo sa voxel sa 15 kamora ho khalemeloa bakeng sa lilemo (khokahano e fapaneng e fapaneng ho thalamus e nepahetseng, e bohareng ba x = 22, y = -25 z = 12, peak r = -0.51, p <0.005, mokhatlo o motle ho gyrus e nepahetseng ea parahippocampal, x = 33, y = -18, z = -26, tlhoro r = 0.54, p <0.005, le mokhatlo o motle oa kantle ho naha o kopaneng, tlhoro x = - 4, y = 7, z = 28.5 r = 0.48, p <0.05), empa ha ho le ea mong ea ileng a pholoha khalemelo e phethahetseng ea boko.
Ho tseba hore na li-subscales tsa ho Batla Novelty ka bomong li amana le [18F] fallypride BPND bohareng ba boko, re ile ra etsa tlhahlobo ea poso ea voxelwise e amanang le sekhahla se seng le se seng. Likhoebo tsohle tsa 4 tsa Novelty-Seeking Scale li bonts'a bonyane likamano tse mpe tse itekanetseng le sebaka sa midbrain sa DA, empa ha ho le o mong o fetang boholo kapa boholo bo hlahisitsoeng ke tlhahlobo ea kakaretso ea Novelty-Searching Score. Bonyane li-voxels tse 15 tse bonts'ang bohlokoa ho p <0.05 li ne li le teng bakeng sa subscale ka 'ngoe (litlhahlobo tse ling tsa tlhahlobo ea Novelty-Seeking subscales li hlalositsoe ka lisebelisoa tsa tlatsetso tsa inthanete, tse fumanehang ho www.jneurosci.org).
Puisano
Lintlha tse teng hona joale li bontša hore litšobotsi tsa batho ba batlang lintho tse ncha ho batho li amahanngoa le ho fumaneha ha D2-joaloka receptor ho SN / VTA. Hobane li-receptor tse kang li-midbrain D2-li-regorec li laoloa ke li-somatodendritic autoreceptors, liphetho tsena li fana ka maikutlo a kamano e ikhethileng pakeng tsa mekhoa ea ho batla lintho tse sa tloaelehang le ho fumaneha ha motho ka boeena. Tlhatlhobo ena e fetoha le liphumano tsa autoinhibition e fokotsehileng litsong tse kholo tsa karabelo tse phahameng (Marinelli le White, 2000).
Hobane DA autoreceptor ke taolo e matla ea bokhoni ba lisele tsa DA ho chesa (Aghajanian le Bunney, 1977; Lacey et al., 1987; Mercuri et al., 1992, 1997; Adell and Artigas, 2004) tofauti tsa motho ka mong autoinhibitory ena mochine oa taolo o ne o ka lebelloa ho lebisa ho phapang e kholo mekhoeng e susumetsang ea li-neuron tsa DA, ka hona ho lokolloa ha DA. Ehlile, litonong ho na le khokahano e fapaneng pakeng tsa litefiso tsa DA tsa ho thunya lisele le hore na ts'ebetso ena e ka hatelloa ke ts'ebeliso ea lehae ea DA (White le Wang, 1984; Marinelli le White, 2000). Liroto tse phahameng tse arabelang tse ngata li bonts'a tšebetso e atisang ho khaoha ea DA e etsahalang khafetsa le e tšoarellang nako e telele ho feta litoeba tse tlase tse arabelang (Marinelli le White, 2000), tse ka hlalosang maemo a maholo a lokolloang ke basal striatal DA a hlokometsoeng ka litoeba tse phahameng tse arabelang. (Bradberry et al., 1991; Piazza et al., 1991a; Hooks et al., 1992; Rougé-Pont et al., 1993, 1998) (Fig. 3). Ntle le ho fana ka maikutlo a mabe ka ho thunya ho matla, liphuputso tsa morao tjena tsa li-neurons tsa DA tse nang le cultured li bontša hore D2-like autoreceptors e susumetsa ts'ebetso ea pacemaker ea lisele tsa DA nakong ea lithuto tse telele, hore batho ba nang le taolo e tlase ea autoreceptor ba ka ba le karolelano e khōloanyane ea ho phatloha. ho thunya mosebetsing oa tonic (Hahn et al., 2006).
Setšoantšo sa 3. Moetso oa taolo ea autoreceptor le phapang ea motho ka mong ho batleng lintho tse ncha. Ka lebaka la palo ea bona e tlase ea li-somoreodendritic autoreceptors, tokollo ea lehae ea somatodendritic ea DA ho SN / VTA e hlahisa autoinhibition e le 'ngoe ea seleng ea DA e thunya batho ba bangata ba sa tsebeng letho ba batlang boqapi.
Ka lebaka leo, batho ba batlang bo-ralitaba ba phahameng ba lokolla li-DA tse eketsehileng libakeng tsa sepheo sa axon ha li susumetsoa ke lintho tse ncha kapa maemo a mang a etsang hore lisele tse bohareng tsa DA li tuke.
Karolo e ikhethang ea taolo ea autoreceptor ea DA ho susumelletseng boits'oaro ba ho batla lintho tse ncha e kanna ea bonts'a bokhoni bo ikhethang ba tšusumetso e ncha ea ho baka ho thunya ha SN / VTA (Ljungberg et al., 1992). Lithuto tse tharo tsa morao-rao tse sebetsang tsa MRI li hlokometse likarabo tsa mali tsa oksijene ea mali (BOLD) sebakeng sa SN / VTA ha batho ba phetseng hantle ba ne ba lebelletse kapa ba shebile litšoantšo kapa mekhatlo ea lipale (Schott et al., 2004; Bunzeck le Düzel, 2006; Wittmann et al., 2007). Mohlomong sena se bonts'a ho phatloha ha lisele tsa DA ho arabela mokhoa o mocha. Kakade le Dayan (2002) ba fana ka maikutlo a hore mofuta ona oa ho thunya ka mokhoa o sa tloaelehang oa li-neuron tsa DA o fana ka "bonase ea ho lekola" e khothatsang e khothalletsang phuputso ea tikoloho kapa tikoloho. Ho ipapisitsoe le tlhaiso-leseling eo re nang le eona hona joale, batho ba nang le maemo a tlase a autoreceptor ba ne ba tla boleloa esale pele hore ba tla ba le "bonase ea lipatlisiso" e kholo ho feta ba nang le maemo a phahameng a autoreceptor.
Lintlha tse ntseng li eketseha liphoofolong tsa batho le tsa batho bao e seng batho li bontša hore mollo oa methapo ea methapo ea methapo ea DA e arabela mehopolong ea moputso le meputso e sa lebelloang, kapa e boletsoeng esale pele (Schultz le Dickinson, 2000; O'Doherty et al., 2002; Bayer le Glimcher, 2005; D Ardenne et al., 2008; Murray et al., 2008). E le sepheo se seholo sa likhakanyo tsa VTA, ventral striatum ka mokhoa o ts'oanang e bonts'a ts'ebetso e eketsehileng hammoho le meputso le liphoso tse nepahetseng tsa ho bolela esale pele (Berns et al., 2001; O'Doherty et al., 2002; Pagnoni et al., 2002; Knutson le Adcock, 2005; Abler et al., 2006; Yacubian et al., 2006). Ka 'nete, boholo ba likarabo tsa BOLD tsa striatal tse hokahantsoeng le liphoso tsa ho bolela esale pele li hlophisoa ke mekhoa e hlophisehileng ea DA (Pessiglione et al., 2006). Ha ho fanoa ka tlhaiso-leseling e teng mabapi le ho batla lintho tse ncha le taolo ea taolo ea DA, ho latela hore ba batlang lintho tse ncha ba tla ba le ntlafatso ea likarabo nakong ea maemo a lokollang DA. Tumellanong le khopolo ena, Abler et al. (2006) haufinyane e bontšitse hore batho ba ipehelang lintlha tse holimo ho tlhahlobo ea excitability subscale (NS1) ba bonts'a likarabo tse kholo tsa BOLD ho feta ba fanang ka lintlha tse tlase ha ba pepesetsoa liphoso tse nepahetseng tsa ho bolela esale pele. Kahoo, phapang pakeng tsa maikutlo a batho ka bohona e ka lebisa ho karabelo tse fapaneng feela lithutong tse ncha, empa ho tse ngata tse fapaneng tsa ts'usumetso le ho ithuta tse itšetlehileng ho DA.
Karolelano pakeng tsa litšobotsi tsa botho bo batlang bo-rasaense le ts'ebetso ea autoreceptor le tsona li ka baka tlokotsi e matla ea ho lemalla ha batho ba batlang bocha. Ka litoeba, baetsi ba lipotso tse phahameng tse phahameng ba bonts'a ho lokolloa ha DA ho arabela li-psychostimulants (Hooks et al., 1991, 1992). Le ha kamano e pakeng tsa DA midbrain BPND bakeng sa [18F] fallypride le karabelo ho li-psychostimulants ho batho e sa tsejoe hona joale, lithuto tse 'maloa li tlalehile kamano pakeng tsa ho batla tse sa tloaelehang le likarabo ho amphetamine, ka batho ba bangata ba batlang bocha ba bontšang karabelo e ntlafalitsoeng ea kelello le psychophysiological ho D-amphetamine (Sax le Strakowski, 1998; Hutchison et al., 1999). Ka mokhoa o ts'oanang, Leyton et al. (2002) e tlaleha khokahano pakeng tsa Ho Batla Novelty le palo ea tlhahiso ea DA ea amphetamine (e lekantsoeng le [11C] raclopride kuhamisoa) ho ventral striatum ka sampole e nyane ea lithuto tsa motho tse phetseng hantle. Boileau et al. (2006) e boetse e bonts'a hore ho batla bocha ho bolela esale pele hore na maikutlo a ntlafatsang a tla hlaha ka litekanyetso tse pheta-phetoang tsa amphetamine. Liphetho tsena ka bobeli e ka ba sephetho se tobileng sa taolo e tlase ea autoreceptor e amanang le ho batla lintho tse ncha.
Lintlha tse teng hona joale li siea potso ea hore na hobaneng ho na le phihlello e tlase ea "midbrain D2-receptor" ho batho ba batlang lintho tse ncha. Karabo ea potso ena e amana ka kotloloho le tlhaloso ea rona ea litlamorao tsa ts'ebetso ea ho theola D2-joaloka BPND. Monyetla o mong ke hore ho na le karolelano e theotsoeng ea li-autoreceptor ho li-neuron tsa DA, joalo ka hore ho na le taolo e fokolang ea autoreceptor bakeng sa neuron e ngoe le e ngoe ea DA. Sena se tla tsamaellana ka kotloloho le mefuta ea liphoofolo. Leha ho le joalo, ho na le litlhaloso tse ling tse peli tse ka bang teng tse sa lumellaneng le tlhaiso-leseling ea liphoofolo, empa leha ho le joalo li hloka ho nahaneloa. Taba ea mantlha, ho fumaneha ha li-autoreceptor tse theotsoeng ho ka hlaha haeba karolelano ea li-autoreceptor ho li-neuron tsa DA e tloaelehile, empa ba batlang lintho tse ncha ba na le li-neuron tse fokolang tsa DA. Sena se ka lebisa ho theoeng ka kakaretso ha ts'ebetso ea DA, ho fapana le ho fokotsa taolo ea autoreceptor. Leha ho le joalo, hona ha ho lumellane le tlhaiso-leseling e bonts'ang hore bakuli ba Parkinson (ba nang le bothata ba ho fokotsoa ha li-neuron tsa DA) ba theotse litšobotsi tse ncha tsa ho batla botho (Menza et al., 1993; Fujii et al., 2000). Ntle le moo, khopolo-taba ea ho theola methapo ea kutlo ea DA ha e lumellane le lingoliloeng tse nang le litoeba tse bontšang hore ba arabelang ka mokhoa o phahameng ba phahamisitse maemo a DA a kantle ho sele ho striatum (Bradberry et al., 1991; Piazza et al., 1991a; Hooks et al., 1992 ). Monyetla oa bobeli ke hore phumaneho e theotsoeng ea autoreceptor ho ba batlang lintho tse ncha e tsoa ho liphapang tsa maemo a DA a sa feleng. [18F] Fallypride BP e bohareng ba boko e susumetsoa ke maemo a DA a sa feleng, joalo ka hore keketseho ea li-extracellular DA li lebisa ho [18F] fallypride BPND, mme e fokotseha maemong a kantle ho lisele tsa DA a eketseha [18F] fallypride BPND (Riccardi et al., 2006 , 2008). Na batho ba batlang lits'oants'o tse phahameng ba ka be ba theotse ho fumaneha ha li-autoreceptor hobane ba ekelitse li-endo native extracellular DA level in the midbrain, e lebisang mosebetsing o moholo oa li-autoreceptor tsa bona? Le ha ho khonahala, hona ho bonahala ho se bonolo joalo ka tlhaloso e le 'ngoe. Phapang lipakeng tsa SN's BPND lihloohong tsohle e kholo ho feta phetoho ea BPND e susumetsoang ke lits'ebetso tsa pharmacologic tse fetolang maemo a DA a extrasynaptic (Riccardi et al., 2006, 2008). Ho feta moo, leha ba na le kutloelo-bohloko maemong a DA a sa feleng, boholo ba phapang lipakeng tsa BPND ho batho ka bomong e lula e le teng nakong ea lits'ebetso tsena tsa pharmacologic. Mohlala, ho hlahlojoa bocha hoa sebaka sa tlhaiso-leseling e tsoang ho thuto ea Riccardi et al. (2008), moo maemo a DA a neng a le maemong a tlase a theotsoeng ka -methyl-para-tyrosine, a bonts'a hore 75% ea phapang ea SN BPND seterekeng se felileng e hlalositsoe ke BPND seterekeng se senang letho. Sena se bolela hore bonyane ho bankakarolo ba bophelo bo botle ba kelello, maemo a amanang le methapo ea methapo ea mmele a lulang a le teng a lula a le teng khafetsa ho sa tsotellane le litlolo tsa bongaka ba meriana tse fetolang maemo a DA a atolositsoeng. Ka hona, ho bonahala eka ha ho na monyetla oa hore phapang e kholo ho [18F] fallypride BPND lithutong tsohle e ka hlalosoa ka mokhoa o ikhethileng ho latela maemo a holimo a holimo ho DA.
Lintlha tse peli tse eketsehileng tsa mokhoa li tiisa ho nahanisisa ka liphetho tsa hona joale. Taba ea pele, lithuto tsa PET bathong li haelloa ke ho rarolla libaka, e leng ho etsang hore ho be thata ho hlakisa boholo ba ho kenya letsoho ha VTA le SN. Tsepamiso ea lingoliloeng tsa liphoofolo ka tlhaho e bile VTA e fuoeng merero ea eona ho proven striatum. Leha ho le joalo, ho se tšoane ha lintlha tsa motho ka mong tse ka amang maemo a marang-rang le VN le SN (bona puisano ka lisebelisoa tse tlatsetsang marang-rang tse fumanehang ho www.jneurosci.org). Kahoo, leha ho na le tharollo e phahameng ea sebaka ha ho hlake hore na sebaka se ikopantseng se ne se ka thibeloa ho VTA. Taba ea bobeli, hore na sephetho se hlahisa litholoana life e le D2, D3, kapa li-subtypes ka bobeli. Le ha li-receptor tsa D3 li sa atamelehe ho feta li-receptor tsa D2, phuputso ea morao-rao e fumanoeng e fokolitse li-receptor tsa D3 tse sebetsang ka har'a midbrain ea li-rodent tse phahameng tse arabelang tse ngata (Pritchard et al., 2006). Ka bomalimabe, li-radioligand tse khethehileng li tla hlokahala ho khetholla menehelo e lekanyelitsoeng ea D2 le li-receptor tsa D3 ho batla ho sa tloaelehang bathong.
Ka bokhuts'oanyane, tlhaiso-leseling e teng hona joale e bonts'a khokahano e makatsang lipakeng tsa litoeba le batho kamanong lipakeng tsa lintlha tsa bohareng ba bongoana le litšobotsi tse bonoang tse amanang le bohloeki. Khokahano ena e hlahile leha e le 'nete ea hore re ile ra lekola bocha ba ho batla tlaleho ea boikoetliso e tlisoang ke ho khetha litaba tse ncha, athe lithuto tsa litheko li tloaetse ho lekanya likarabo maemong a rileng a ke keng a qojoa. Hona ke phapang e bohloko ea hore likarabo ho li-novelty tse ke keng tsa qojoa ha li hokahane haholo le likhetho tsa nnete tsa litoeba (Klebaur et al., 2001; Kaelo et al., 2004; Zhu et al., 2007) 'me li ka amana le corticosterone Karabelo ea khatello ea maikutlo (Piazza et al., 1991b; Rougé-Pont et al., 1998). Re hakanya hore lintlha tsa DA tsa ho ikamahanya le maemo li susumetsa likarolo tse ngata tsa kamoo libopuoa li arabelang ho bocha le moputso, le hore liphapang tse fapaneng ho mabaka ana li bonahala ka ho fetellana, ho sa tsotelleng mekhoa e sa tloaelehang le e bohale ho pholletsa le mefuta.
Mongolo o botlaaseng ba leqephe
E amohetse May 28, 2008; Oct. 14, 2008; e amohetsoe Nov. 5, 2008.
Mosebetsi ona o tšehelitsoe ke National Institutes of Health Grant 1R01 DA019670-02.
Litaba li lokela ho lebisoa ho Dr. David H. Zald, Lefapha la Psychology, PMB 407817, 2301 Vanderbilt Place, Nashville, TN 37240. Email: [imeile e sirelelitsoe]
Copyright © 2008 Mokhatlo oa Neuroscience 0270-6474 / 08 / 2814372-07 $ 15.00 / 0
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