Liphuputso tsa positron tse hlahisoang ke tomography ea li-dopamine receptors tse nang le lithethefatsi tse tloaelehileng (2008)

Philos Trans R Soc Lond B Biol Sci. Oct 12, 2008; 363 (1507): 3223-3232.

E phatlalalitsoe marang-rang Jul 18, 2008. Doi:  10.1098 / rstb.2008.0092

PMCID: PMC2607324

Sehlooho sena se bile teng e boletsoeng ke lihlooho tse ling ho PMC.

Eya ho:

inahaneloang

Mefuta ea liphoofolo e fane ka tlhaiso-leseling ea bohlokoa e amanang le tšobotsi le maemo a mmuso a amanang le ho ba kotsing ea ho lemalla lithethefatsi. Lithuto tsa rona tsa ho nahana ka likelello tsa litšoene li khahlile D2 ba amohelang bokhoba ba koae. Mohlala, kamano e sa lumellaneng pakeng tsa D2 ho fumaneha ha li-receptor le litekanyetso tsa ho itaola tsa koae ho se ho tlalehiloe. Ntle le moo, mefuta ea tikoloho, joalo ka e amanang le sebopeho sa maemo a phahameng sechabeng, e ka ama ho fumaneha le kutloelo-bohloko litlamorao tse amanang le tlhekefetso ea koae. Ka mokhoa o ts'oanang, bobeli ba D2 ho fumaneha ha li-receptor le ho itlhompha ka koae ho ka fetoloa ke tsamaiso ea lithethefatsi tse sa foleng le ho feto-fetoha ha maemo ho li-hormone. Ntle le moo, boikoetliso ba koae bo ka fetoloa ka mokhoa o laolehileng ka khatello ea khatello ea maikutlo, joalo ka ho kenella sehlopheng sa batho ba sa tsejoeng, se ka fetolang tekanyetso ea "cocaine-curve" ka letsohong le letšehali ho litšoene tse ling le ho tokelo ea liphoofolo tse hlahelletseng, ho fana ka maikutlo a tšebelisano lipakeng tsa maemo a bophelo le khatello e matla ea maikutlo. Ka lehlakoreng le leng, ho sa natsoe maemo a maemo sechabeng, ho ruisa haholo tikoloho, joalo ka ho eketsa boholo ba sebaka sa bolulo, e fetisetsa karohano ea karohano ea koae ka ho le letona. Liphumano tsena li bonts'a tšusumetso e atileng ea tikoloho ho fetoleng litlamorao tse matlafatsang tsa koae le ho kenya letsoho ka matla bokong D2 li-receptors.

Keywords: dopamine, D2 li-receptors, boits'ebetso ba koae, boitšoaro ba sechaba, mefuta ea liphoofolo, mofuta oa batho bao e seng batho

1. Selelekela

Ts'ebeliso e mpe ea lithethefatsi e tsoela pele ho ba bothata bo boholo ba bophelo bo botle ba sechaba lefats'eng ka bophara (WHO 2004). USA, batho ba ka bang limilione tse 2.9 ba lilemo li 12 kapa ho feta ba sebelisitse lithethefatsi tse seng molaong ka lekhetlo la pele ho 2005, ka likhakanyo tsa morao-rao tsa Maamerika a limilione tse 2.4 tse netefatsang tšebeliso ea koae ea hona joale (SAMHSA 2006). Ka har'a European Union, boiphihlelo ba nako ea bophelo ba motho ka koae ea banna ba lilemo li 15-24 bo tlalehiloe ho 5-13% (WHO 2004). Ho 2001, 56% ea linaha tsohle tse tlaleha ka mekhoa ea koae e tlalehiloe e eketseha; Europe, palo eo e ne e le 67% (WHO 2004). Hajoale ha ho na mekhoa ea phekolo e amoheloang ea ho lemalla koae, le ha ho ntse ho nahanoa ka mekhoa e mengata ea lipale. O'Brien 2005; Elkashef et al a. 2007). Morero o moholo oa lenaneo la ho etsa lipatlisiso le hlalositsoeng tlhahlobisong ena ke ho lekola boits'oaro, litokelo tsa bongaka le methapo ea kutlo, ho li boloka le ho khutlela mokhoeng oa ho lemalla koae ka mefuta eo e seng ea batho. Leano lena la ho etsa lipatlisiso le tiisa hore kutloisiso e ntle ea mefuta ena e ka lebisa ho maano a ntlafalitsoeng a ho lemalla koae.

Joalokaha ho boletsoe ke James Mills ho 1965, '[A] ny lefu - ho kenyelletsa le tšebeliso ea lithethefatsi-ho latela litheko tsa tsona tse tharo: motho ea tšoaelitsoeng, ntho e tšoaetsang le tikoloho eo ba babeli ba ka kopanang ho eona'. Haufinyane, 'litlhoko tsena' li hlalositsoe ho latela 'moemeli', 'moeti' le 'moelelo' (O'Brien 2006). Thutong ena, re tla hlalosa hore na lintho tsena tse tharo li nkuoa joang ho nts'etsopele maano a phekolo ea mofuta oa tlhekefetso ea koae. Ha re shebana le koae, ke khopolo ea rona hore maano ana, a totobatsang maemo a bophelo le maemo a tikoloho, a sebetsa bakeng sa lithethefatsi tsohle tsa tlhekefetso.

(a) Moemeli

Cocaine ke moemon agonist ea sa sebetseng, ea kopanang le tumellano e lekanang ho dopamine (DA), serotonin (5-HT) le ba tsamaisang thepa ea noradrenaline (Ritz et al a. 1987; Woolverton le Johnson 1992). Boholo ba lithuto tse mabapi le mehato ea ketso e nkang karolo ea tlhekefetso e phahameng ea ts'ebeliso ea koae e shebile haholo tsamaisong ea DA. Ka bokhutšoanyane, lisele tsa DA ho tsoa morerong oa tikoloho e arohaneng ho ea ho meaho kahare, ho kenyelletsa le li-bokono, le morero ho cortex (Haber & McFarland 1999); Litsela tsena li bile le tšusumetso ho boits'oarbo bo botle bohle (Di Chiara le Imperato 1988). DA e lokollotsoeng ka har'a phokotso ea mantsoe e tlosoa ke phetoho e sebetsang ke morekisi oa DA. Cocaine e sebetsa ka ho thibela morekisi le ho phahamisa maemo a DA a tsoang kantle ho naha, a hlahisang litlamorao tsa ona ka ho tlama malapa a mabeli a hlasimolohileng a li-receptors tsa DA, D1- le D2- Lisebelisoa tse fumanehang (Monate et al a. 1993). Mosebetsi oa ho nahana ka litšoantšo o hlalositsoeng tlhahlobo ena o tla shebana le D2Lisebelisoa tse kang lisebelisoa le lisebelisoa tsa ho nahana, [11C] raclopride le [18F] fluoroclebopride (FCP), e sa khetholle har'a karolo e ka tlase ea D2 ka mahlohonoloMach et al a. 1993). Taba ea bohlokoa ke hore na D2 positron emission tomografics (PET) ligands li hlahloba pele ho kapa postynaptic D2-e kang li-receptors. E ipapisitse le mosebetsi oa lesioningChalon et al a. 1999), re kholoa hore liphetoho tse ho D2 ho fumaneha ha li-receptor ho hlile ho bakoa ke liphetoho ho postynaptic D2 ts'ebetso ea li-receptor (bona Nader & Czoty 2005).

Patlisiso ka har'a pharmacodynamics le pharmacokinetics ea cocaine e lebisang ho matla a eona a tlhekefetso e matlafalitse kutloisiso ea rona ea sistimi ea DA le mekhoa ea moputso. U sebelisa mekhoa e joalo ka Ka vivo Micracalalysis liphoofolong tse kentsoeng ka mokhoa o hlakileng oa cannulae e lebisang likarolong tse fapaneng tsa boko, cocaine e bontšitsoe ho phahamisa maemo a DA a tsoang libakeng tsa boko tseo ho lumeloang hore li sebetsa pakeng tsa tšebetso (bona. Bradberry 2000; Czoty et al a. 2002; Howell le Wilcox 2002). Ho batho, ho sebelisa mekhoa e sa hlaseleng ea ho nahana ka boko joalo ka PET, kamano e lipakeng tsa ho phahamisa DA le litlamorao tse matla tsa lithethefatsi e ile ea hlahlojoa (Volkow et al a. 1999). Thutong eo, bafuputsi ba tsamaisitse [11C] raclopride, e tlamellang ho postsynaptic DA-D2 receptors, le ho lekanya ho fallisoa ha radiotracer eo ke DA ho batho ba sa sebeliseng lithethefatsi hampe. Hobane cocaine e ne e ke ke ea fuoa batho bana ka mabaka a boitšoaro, bafuputsi ba sebelisitse agonist e 'ngoe e sa sebetseng ea DA, methylphenidate, e nang le litlamorao tse matla ho liphoofolo le batho (mohlala, Johanson le Schuster 1975; Volkow et al a. 1999). Ho ne ho na le kamano e hlophisehileng lipakeng tsa bokhoni ba methylphenidate ho phahamisa DA le ho lahla [11C] moraro ho tloha D2-e tšoanang le li-receptors le botebo ba litlaleho tse tlisoang ke "e phahameng". Habohlokoa, lithutong tse sa tlalehang e phahameng, methylphenidate ha e phahamise DA.

Qetellong, leha ho na le bohlokoa bo hlakileng ba liketso tse ikhethang tsa cocaine libakeng tsa sepheo sa methapo ea kutlo, ho bohlokoa ho supa hore ke lebaka la rona hore litlamorao tse tummeng tse amanang le tlhekefetso ea koae ha li hlalosoe feela ke tšebelisano ea pharmacological lipakeng tsa lithethefatsi le li-receptor. Ho na le phapang e hlakileng litlamorao tsa boitšoaro ba koae ha e fanoa ntle le khang ke mofuputsi khahlanong le boits'oaro bo laoloang ke phoofolo (Dworkin et al a. 1995; Stefanski et al a. 1999; Bradberry 2000). Ho feta moo, joalo ka ha ho hlalositsoe ka botlalo ka tlase, kemiso ea ho fumaneha ha koae e ka ba le litlamorao tse kholo ho litlamorao tsa koae.

(b) Moamoheli

Lithuto tse hlalositsoeng ka tlase li sebelisitse litloholoana tseo eseng tsa batho, haholo-holo, litšoene tsa rhesus (Macaca mulatta) kapa litšoene tsa cynomolgus (Macaca fascicularis). Hona le litšoene tsena, litšoene tsena tsa Lefatše la Khale ke mefuta e amanang haholo le phylogenet ka tlhaho ho batho e ka sebelisoang lipatlisiso tsa biomedical. Kahoo, bokhoni ba rona ba ho akaretsa ka nepo mehlala ea liphoofolo tse sebelisanang le lithethefatsi hampe bo matlafatsoa ka ho sebelisa litšoene e le lithuto; hona ho bohlokoa haholo lithutong tsa ho nahana (Nader & Czoty 2008). Ho na le liphapang tse tlalehiloeng lipakeng tsa litšoelesa tsa monkey le rodent dopaminergic (Berger et al a. 1991; Joel le Weiner 2000), ho kenyelletsa phapang pakeng tsa tumellano ea DA ho D1- le D2- Lisebelisoa tse fumanehang (mahola et al a. 1998), hammoho le bopaki ba phapang ea mefuta ea liphetoho tse hlahisitsoeng ke koae ka ts'ebetso ea boko (mohlala Lisona et al a. 1996) le litlamorao tsa boits'oaro ba li-agonist tsa DA tse sa sebetseng ho kenyelletsa koae (mohlala Roberts et al a. 1999; Lile et al a. 2003). Ho boetse ho na le data e bonts'ang hore lithethefatsi tse ngata, ho kenyeletsa le lithethefatsi tsa tlhekefetso, li na le profiles e ts'oanang ea pharmacokinetic ho litšoene le batho, tse fapaneng ka litoeba (mohlala. Banks et al a. 2007;; bona Weets et al a. 2007 bakeng sa tlhahlobo).

Litšoene li boetse li lumella ho etsoa lipatlisiso tsa mefuta e meng ea sechaba tlhekefetsong ea koae (Morgan et al a. 2002; Czoty et al a. 2005); lithuto tsena li fana ka karolo e ikhethang ea phetolelo lipatlisisong tsa rona. Mokhahlelo oa kahisano (ke hore, maemo a sechaba ka 'ngoe ea litšoele tse' ne ho sehlopha) e khethoa ke ho rekota ba hapileng lintoa lipakeng tsa litšoene (Kaplan et al a. 1982). Tšoene ea pele ('e hlahelletseng') e hlalosoa e le tšoene e loantšang litšoene tse ling tse tharo. Monkey ea boemo ba bobeli e hapa lintoa tsohle ntle le khahlanong le tšoene ea boemo ba pele, joalo-joalo. Tšoene e loantšang lintoa le ba bang kaofela ka pene e bitsoa monkey e nang le maemo a tlase haholo ('subordinate').

Ho etsa thobalano ke taba e atileng eo ho sa tsotelleloeng lipatlisiso tsa tlhekefetso ea lithethefatsi. Ha boholo ba lipatlisiso tsa rona bo tsepamisitse maikutlo lithutong tsa banna, ho na le bopaki bo ntseng bo hola ba phapang ea thobalano boits'oarong, pharmacology le liketsong tsa neurochemical tsa lithethefatsi tse hlekefelitsoeng (Lynch et al a. 2002; Lynch 2006; Terner & de Wit 2006). Habohlokoa, liphapang tsena tse tlalehiloeng tsa thobalano li fetela ka nqane ho ts'ebeliso e mpe ea lithethefatsi ho kenyelletsa mathata a mangata a kelello ho kenyelletsa schizophrenia, lefu la Parkinson le khatello ea maikutlo e tlamang (mohlala Seman 1996; Walk et al a. 2003). Lithutong tsa basali, ho na le bopaki ba hore karolo ea potoloho ea khoeli e ka fetola kutloisiso ea lithethefatsi tsa tlhekefetso (bona Terner & de Wit 2006). Li-macaque tsa basali li na le potoloho ea matsatsi a ho ilela khoeli ea 28, ka ho feto-fetoha hoa maemo ho estrogen le progesterone e tšoanang le ea basali (mohlala, Jewitt & Dukelow 1972; Appt 2004), Ho li etsa tse loketseng ho ithuta maemo a amanang le bophelo bo botle ba basali. Le ha ho sa buuoe ka eona pampiring ena, lithuto tse amanang le ho pepesetsoa lithethefatsi ke bakhachane le tsona li tla una molemo ka ts'ebeliso ea litloholo tseo e seng batho. Mohlala, nako ea bokhachane ho li-macaque e ka ba likhoeli tse ts'eletseng, e haufi le kemolo ea motho ebile e telele ho feta mefuta ea litoeba (Sandberg le Olsen 1991).

Mabapi le sehlooho sa tlhahlobo ena, haufinyane re fuputse hore na karolo ea mekhahlelo ea menstrual e nkile mehato ea DA-D joang2 ho fumaneha ha litšoelesa tsa basali cynomolgus (Czoty et al a. 2008). Joalokaha ho tla hlalosoa ka tlase, ho bonahala ho na le kamano lipakeng tsa D2 ho fumaneha ha receptor le litlamorao tse matlafatsang tsa koae. Kahoo, haeba karolo ea potoloho ea khoeli e ama D2 maemo a receptor, ona e ka ba mokhoa oa mantlha oa phapang litlamorao tse amanang le tlhekefetso ea koae (kapa lithethefatsi tse ling tse hlekefetsoang) ho basali ba lekiloeng ka linako tse fapaneng tsa khoeli (Sofuoglu et al a. 1999). Lithuto tse tharo tsa ho nahana ka PET ho basali li fuputse D2 ho fumaneha ha li-receptor e le ts'ebetso ea potoloho ea ho ea matsatsing; ho tlalehiloe liphetho tse tharo tse fapaneng. Wong et al a. (1988) e tlaleha tloaelo e lebisang ho ts'oaroeng ho tlase hoa radiotracer seterekeng sa basali ba lekiloeng sethaleng sa follicular bapisoa le luteal phase. Phuputsong e sa tsoa feta, ba fumane D2 mehato ea li-receptor ho putamen (empa eseng caudate nucleus kapa ventral striatum) ho basali ba sethaleng sa luteal le karolo ea follicular (Munro et al a. 2006). Qetellong, Nordstrom et al a. (1998) ha a fumane bopaki ba ho fapana ha linako tsa ho ilela khoeli ho D2 ho fumaneha ha li-putamen ho basali ba bahlano. Ho na le lintlha tse 'maloa tse ka bakang sephetho sena se fapaneng, ho kenyeletsa boemo ba khatello le nalane ea lithethefatsi ea basali. Ho bohlokoa, lintlha tsena li ka laoloa lithutong tsa liphoofolo. Ho litšoene tse supileng tse tloaelo tsa ho leka, tse tloaetseng ho palama li-cynomolgus tsa basali, re fumane hore D2 ho fumaneha ha li-receptor e ne e le ka mokhoa o tebileng (approx. 13%) tlase karolong ea follicular ha e bapisoa le litšoene tse tšoanang tse ithutoang nakong ea karolo ea luteal (Czoty et al a. 2008). Phello e joalo e ts'ehetsa phapang ea kutloisiso ea litlamorao ho litla-morao tsa lithethefatsi maemong a fapaneng a potoloho ea khoeli le khoeli mme e totobatsa bohlokoa ba matla a ho phahama ha lihormone e le sesosa sa ts'ebeliso e ka bang le litlamorao tsa lithethefatsi tse sebelisitsoeng hampe. Ntle le moo, datha tsena li fana ka maikutlo a hore lithuto lithutong tsa basali li lokela ho fokotsa tšusumetso ea ho fetoha ha potoloho ea khoeli ka ho nka mehato maemong a tšoanang a potoloho ea ho ea matsatsing ha ho etsoa lithuto tse telele.

(c) Moelelo oa taba

Lithutong tsa rona, re nka taba e potoloha e akaretsa maikutlo ohle a tikoloho, nalane ea teko le boemo ba sechaba. Bakeng sa pampiri ena, re tla fokotsa moelelo oa litlhaloso tse khutšoane tsa mehlala e sebelisitsoeng ho lekola ntlafatso ea koae le boitšoaro bo sa rateheng ba batho bao e seng ba batho. Ha o hlalosa mefuta ea ts'ebetso ea lithethefatsi mabapi le kemiso ea matlafatso, phapang e bohlokoa e lokela ho etsoa lipakeng tsa ho matlafatsa 'litlamorao' le ho matlafatsa 'matla'. Tšusumetso e matlafatsang e bolela feela hore karabo e lebisang tlhahiso ea lithethefatsi e etsahala ka litheko tse phahameng ho feta ho araba ho hlahisa tlhahiso ea koloi. Bakeng sa moriana o mong le o mong o nang le litlamorao tse matlafatsang, sebopeho sa li-do-reaction curve se lekana le sebopeho sa U-inverted. Ka mantsoe a mang, ho na le leoto le nyolohang le khetholloang ka karabo ea tekanyetso ea hore u arabe, tekanyetso e hlahisang litheko tse phahameng tsa karabelo le leoto le thellang moo litheko li nyolisang lipalo tse tlase tsa bona (bona Zernig et al a. 2004). Hobane lintlha tse 'maloa li susumetsa sebopeho sa khefu, ho ka se khonehe ho bapisa li-curve tsa karabelo ea li-drug tse fapaneng le ho bua polelo e amanang le hore na lithethefatsi li "matlafatsa haholo" joang (Woolverton le Nader 1990). Leha ho le joalo, likemiso tse ling li ka sebelisoa ho etsa liteko tse amanang le ho matlafatsa matla; tsena li tla hlalosoa ka botlalo ka tlase. Ntlha ea bohlokoa eo re lokelang ho e hlakisa ke hore mananeo a fapaneng a ntlafatso a na le lintlha tse a fang tse loketseng ho araba lipotso tse fapaneng ka litlamorao tsa boitšoaro ba koae. Mohlala, lipotso tse amanang le bohlokoa bo lekanyelitsoeng ba ho batla lithethefatsi (ke ho sebelisa k'hok'heine feela) le tšebeliso ea koae ka ho felletseng ka ho hlahisa liphetoho bokong ho ka hlahlojoa ka ho ithuta linako tse fapaneng tsa taolo ea koae. Phapano e joalo e bohlokoa ka ho hlaka ha ho nahanoa ka mekhoa ea kalafo bakeng sa ts'ebeliso e mpe ea lithethefatsi-na ho na le taba hore na mokuli o nkile lithethefatsi tse kae kapa hore na o sebelisitse lithethefatsi nako e kae? Volkow et al a. (1999) e fumane hore maemo a DA-D2 ho fumaneha ha li-receptor joalo ka ha ho lekantsoe le PET ho ne ho its'etleha haholo holima nako ea ts'ebeliso ea koae ho feta ka tekanyo ea lithethefatsi tse sebelisitsoeng pele ho thuto. Phuputso ena e bonts'itse hore boits'oaro bo lebisang ho rekiseng lithethefatsi, bo ikemetseng ho k'hemiste ea koae, bo ka kenya letsoho phetohong e fumanoeng ea ho fumaneha ha DA ho ba hlekefetsang koae le ho ts'ehetsa maikutlo a hore tikoloho e ka ba le litlamorao tse kholo bokong.

Ts'ebeliso ea li-primates tseo e seng batho, lipalo tsa PET le linako tse fapaneng tsa ntlafatso li file monyetla oa ho lekola ka kotloloho bohlokoa ba tšebeliso ea lithethefatsi khahlanong le tšebeliso ea koae ka botlalo (Czoty et al a. 2007a,b). Ho etsa liteko ka kotloloho ena, litšoene tsa 12 tse sa sebetseng li ile tsa amohela scales tsa PET tsa mantlha li sebelisa D2 receptor ligand [18F] FCP. Tse tšeletseng tsa litšoene tsena li ile tsa fuoa koetliso ea ho sebelisa k'hok'heine ka tlas'a kemiso ea tatellano ea bobeli, kemiso e matla ea ts'ebetso eo ho eona ho ts'oaroa ha lithethefatsi ho neng ho bolokoa ka tlhahiso ea maemo a phetseng nakong eohle ea metsotso ea 60 ho fihlela cocaine e qeta ho fanoa.Katz 1980). Tlas'a likhakanyo tsa kemiso ea ho qetela, karabelo ea pele kamora 3mets: nakoana e lekanyelitsoeng; FI 3min) e hlahisitse phetoho ea ts'usumetso (S) e amanang le ntlafatso ea koae le FI ea leshome e felisitsoeng (ke hore, XIUMX e lekantsoeng) e hlahisitse tlhahiso ea koae (e khethiloeng ke FR 10 [FI 10)mets: S]). Nako e fela ka mor'a liente tse peli tsa koae (0.1mgkg-1ente-1). Kahoo, liphoofolo tsena li ne li e-na le nalane e batsi ea ho batla lithethefatsi, empa e le tse tlase haholo tsa "cocaine". Sehlopha sa bobeli sa litšoene tse tšeletseng se ile sa koetlisetsoa ho arabela tlasa kemiso ea FR 30 ea tlhahiso ea koae. Maemo a sehlopha sena a ne a hlophiselitsoe ho etsa mohlala oa 'ho itlopa joala' - litšoene li ka fumana liente tsa 30 tsa 0.3mgkg-1 cocaine habeli ka letsatsi, matsatsi a 2 ka beke. Kahoo, ka lebaka la sehlopha se seng sa litšoene, sehlopha sena sa lithuto se ile sa fumana koae haholo empa ho batla lithethefatsi e ne e le matsatsi a 2 feela ka beke. Re fumane hore ho itlopa bolutu ka koae ho hlahisitse phokotso e kholo ho D2 ho fumaneha ha li-receptor ka nako e 'ngoe le e' ngoe ea nako, ha 'ho batla lithethefatsi' tlasa lenane la li-odara tsa bobeli ha hoa ka ha ama D2 ho fumaneha ha receptor ho feta selemo sa 1. Liphumano tsena li fana ka maikutlo a hore phokotso ho D2 phumaneho e bonoang ho batho e ne e le haholo ka lebaka la litlamorao tse tobileng tsa koae maemong a li-receptor tsa DA.

(i) Likamano tsa tikoloho le tikoloho: karolo ea 1

Ho fumana matlafatso ea lithethefatsi ho susumetsoa ke litšobotsi tsa motho (ke hore, litšobotsi tsa sebopeho) hammoho le likarolo tsa tikoloho (mohlala, maemo a naha). E 'ngoe ea lithuto tsa pele tsa kamano ea tšobotsi ea mekhoa ea ho susumetsoa ke matlafatso ea ts'ebeliso ea lithethefatsi e fanoe ke Piazza et al a. (1989) moo lihlopha tse peli tsa likhoto li ileng tsa aroloa ho ipapisitse le ts'ebetso ea locomotor ka har'a lisebelisoa tse bulehileng e le ba arabelang holimo (HR) kapa ba arabelang ka tlase (LR). Likhoto li ne li kengoa ka har'a li-catheter tse kenang kahare mme ba fuoa monyetla oa ho fumana litekanyetso tse tlase tsa d-amphetamine tlasa kemiso ea FR. Ho fumanoe likhoto tsa HR d-amphetamine boithapollo ba litekanyetso tse tlase ho feta likhoto tsa LR. Ts'ebeliso ea lenane lena le bonolo e lumelletsoe ho bonts'a ts'oaetso ea ho ba kotsing ea ho itšireletsa ho latela tšobotsi eo motho a nang le eona ea boits'oaro, e leng, ketsahalo ea locomotor lebaleng le bulehileng.

Haufinyane tjena, lithuto tsa liphoofolo tsa laboratori li ile tsa hlahloba boitšoaro bo amanang le 'ho hloka matla', tloaelo e bonts'itsoeng e le phahameng ho batho ba hlekefetsang koae (Moeller et al a. 2002). Likhoto li tšoauoa ka mokhoa oa ho itaola ka potlako ho feta likhoto tse sa kenelletseng (Dalley et al a. 2007). Perry et al a. (2005) ho sebetsanoa le hore na ho potlaka ho etella tlhekefetso ea lithethefatsi. Phuputsong eo, likhoto li ile tsa koetlisetsoa mokhoa oa ho theola ho lieha ha ho araba ka lever e le 'ngoe ka tlas'a boemo ba tšohanyetso ba FR 1 ho fella ka phumants'o ea lijo hang hang, ha ho arabeloa ka lever e' ngoe tlasa boemo ba tšohanyetso ba FR 1 ho felletseng ha ho tlisoa ha lijo tse tharo li-pellets kamora ho lieha ho fapaneng. Haeba rat e ile ea khetha khetho ea hang-hang, boleng ba ho lieha bo fokotsehile tekong e latelang bakeng sa mofuta o mong; haeba khetho ea ho lieha e khethiloe, boleng ba ho lieha bo ile ba eketseha tekong e latelang. Boleng bo lekanyelitsoeng bo fetotsoe (MAD) bo lekantsoe bakeng sa ngoe le e ngoe ka ho phahamisa boleng bohle ba ho lieha litekong. Joalokaha ho hlalositsoe ke Perry et al a. (2005), MAD e sebelitse joalo ka tekanyo e lekanang ea moo litekanyetso ka ngoe li fokotsang tšehetso ea lijo. Litefiso tse phahameng tsa MAD, tse emelang ho lieha ho lieha, li ne li supa ho ts'oaroa ha tlase, athe litekanyetso tse nyane tsa MAD li bonts'a boits'oaro bo hatellehang haholoanyane. Likhoto li ne li arotsoe ka lihlopha tse peli, tse phahameng le tse tlase (HiI le LoI, ka ho latellana) li ipapisitse le litekanyetso tsa MAD. Ha ho ithutoa koae ka koae, liphoofolo tsa HiI li ile tsa itaola ka potlako le ka maemo a holimo ho feta likhoto tsa LoI. Ha ho kopanngoa, liphuputso tsena li tšehetsa khopolo ea hore ho na le mekhoa ea batho ba rerileng ho sebelisa lithethefatsi hampe mme ba ka e hlahloba ka mekhoa ea liphoofolo.

Sehlopha sa rona se ithutile mekhoa ea ts'ebetso le tšebelisano ea tikoloho mabapi le ts'ebeliso e mpe ea lithethefatsi lithutong tse seng batho ka lilemo tse fetang leshome. Boholo ba lipatlisiso tsa rona bo entsoe ka litšoene tse nang le koae pele li pepesetsoa koae hore li rarolle likheo linthong tsa bongaka. Mohlala, joalo ka ha ho hlalositsoe kaholimo, ba hlekefetsang koae ba na le maemo a tlase a D2 ho fumaneha ha li-receptor ho feta lithuto tse laoloang (Volkow et al a. 1990, 1993; Martinez et al a. 2004) le basebelisi ba sa sebeliseng lithethefatsi ka litekanyetso tse tlase tsa bas2 phumaneho ya receptor e fumane methylphenidate e tiisa le ho feta (Volkow et al a. 1999). Ha ho tsejoe hore na D e tlase2 maemo e ne e le litholoana tsa ts'ebeliso ea koae kapa ntho e neng e le teng pele e bonts'ang kotsi ea ts'ebeliso ea koae. Potso ke hore na D2 ho fumaneha ha li-receptor ke letšoao la ho beha kotsing ea ts'ebeliso e mpe ea koae. Re arabetse potso ena ka kotloloho ka mekhoa e 'meli. Taba ea mantlha, re kopanya basal D2 ho fumaneha ha litšoelesa tsa litšoene tsa koae ka litheko tse latelang tsa ho itlhokofatsa. Taba ea bobeli, re ithutile ka liphetoho tsa D2 phumaneho ea li-receptor ho litšoene tsa cocaine-naive nakong ea selemo sa 1 sa ho fumana hore na matlafatso ea koae e theotse maemo ana (Nara et al a. 2006). Kakaretso ea lintho tse fumanoeng e bontšitsoe ho Setšoantšo sa 1. Pele, litšoene tsa koae li na le "cocaine" naive2 receptor ligand [18F] FCP mme ea koetlisoa ho araba tlasa FI 3lenane la tlhahiso ea lijo. Ha karabelo e ne e tsitsitse, tšoene e 'ngoe le e' ngoe e ne e kengoe ka mokhoa o amanang le catheter e tsoang kahare, lethal dose ea koae (0.2)mgkg-1ente-1) e fetotsoe bakeng sa litekanyetso tsa lijo le likarabo li tlalehiloe. Taba ea bohlokoa ke hore ho ne ho se na thupelo tlas'a paracigm ea koae - litšoene li ne li pepesoa litheko le litekanyetso tsa karabo li tlalehiloe. Re fumane kamano e sa lumellaneng pakeng tsa mantlha D2 ho fumaneha ha li-receptor le litekanyetso tsa ho itaola ka koae (Setšoantšo sa 1a). Litšoene tse nang le D e tlase2 maemo a li-ceptine tse sebelisoang ke li-cocaine ka litheko tse phahameng ha li bapisoa le litšoene tse nang le D e phahameng2 ho fumaneha ha receptor. Liphumano tsena li tšoana hantle le tse hlokometsoeng ke Volkow et al a. (1999) sebelisa ba sa sebeliseng lithethefatsi ntle le lithethefatsi le methylphenidate. Re fumane hape hore, ka nako ea lilemo tsa 1 moo ho sebelisang koae ho eketsehileng,2 ho fumaneha ha li-receptor ho fokotsehile ho sa tsotelehe hore na maemo a pele a D2 Ho fumaneha ha li-receptor e ne e le tsa monkey e ngoe le e ngoe (Setšoantšo sa 1b). Kahoo, ho bonahala eka low D2 ho fumaneha ha li-receptor ho etsa hore motho a hlaselehe habonolo ho matlafatsoang ke koae le ho tsoella ho pepesehela cocaine le ho feta ho fokotsa maemo ao (Nader et al a. 2002, 2006).

Setšoantšo sa 1 

(a) Khokahano lipakeng tsa motheo oa D2 ho fumaneha ha li-receptor le litekanyetso tsa ho itaola tsa koae ho litšoene tsa banna tsa makhopho. (bLintlha tsa boemeli ho tsoa ho litšoelesa tsa monkey e le 'ngoe (R-1241) tse bonts'ang ho ja koae ka bongata le liphetoho tse amanang le D2 ho fumaneha ha receptor. ...

Liphumano tse kaholimo li tšehetsa ka ho hlaka mohopolo oa hore ho na le mefuta ea tlhaho ea tlhaho, molemong ona D2 ho fumaneha ha li-receptor, tse susumetsang ts'oaetso ea tlhekefetso ea koae. Re boetse re shebile phello ea ho fetoha hoa tikoloho ho D2 ho fumaneha ha li-receptor le hore na litlamorao li na le tšusumetso ea ho matlafatsoa ke koae. Pejana mosebetsi o tsoang sehlopheng sa rona o bonts'itse likamano lipakeng tsa D2 ho fumaneha ha li-receptor le boemo ba sechaba ho litšoene tse tšehali, joalo ka hore litšoene tse tlasa tlase li ne li le tlase D2 maemo a maemo ho feta litšoene tse hlaheletseng (Grant et al a. 1998). Ka mor'a moo re ile ra hlahloba hore na D2 ho fumaneha ha receptor e ne e le tšobotsi eo e boletseng boemo ba maemo sechabeng. Bakeng sa lithuto tsena, re sebelisitse li-20 ka mokhoa o hlokang leeme 'me ka bomong re beha litšoene tsa banna ba cynomolgus. Kamora 'basel PET e lekola ho sebelisoa [18F] FCP e ile ea tsamaisoa, litšoene li ne li beoa ka lihlopha tsa litšoene tse nne ka pene mme kamora likhoeli tse tharo li pholositsoe le [18F] FCP (Morgan et al a. 2002). D2 phihlello ea receptor e ne e se lets'oao la maemo bakeng la maemo a bophelo sechabeng. Kamora likhoeli tse tharo tsa bolulo ba sechaba, re bone phello e ts'oanang e tlalehiloeng ke Grant et al a. (1998) ho litšoene tse tšehali tse neng li lutse hammoho ka lilemo tse fetang 3 — litšoene tse ikokobelitseng li ne li le tlase ho D2 ho fumaneha ha li-receptor ha ho bapisoa le litšoene tse hlaheletseng. Leha ho le joalo, e bile teng ka tsela e fapaneng le eo re neng re e lebelletse. Re ne re na le hypothesised hore le tlase D2 maemo a litšoene tse nyane ha a bapisoa le litšoene tse hlaheletseng ka lebaka la khatello ea maikutlo e sa feleng e tšoaroang ke litšoene tse tlasa maemo a tlase (Kaplan et al a. 1982; Shively & Kaplan 1984). Leha ho le joalo, phapang e fetang ea 20% lipakeng tsa litšoene tse busang le tse tlasa thuto thutong ea rona e bile ka lebaka la bohlokoa nyollelo ho D2 ho fumaneha ha li-receptor ho litšoene tse kholo empa ka karolelano ha hoa ka ha fetoha. Tsena li eketseha ho D2 mehato e ne e le ka lehlakoreng le leng le tlalehiloeng lithutong tse ngata tse bonts'ang tšusumetso ea ntlafatso ea tikoloho ts'ebetsong ea DA-ho kenyelletsa le D e eketsehileng2 methapo ea methapo (mohlala boula et al a. 1993; Rilke et al a. 1995; Hall et al a. 1998). Ho ipapisitsoe le lithuto tsena tsa boiketsetso le ho seo re se fumaneng hore ho na le kamano e fapaneng pakeng tsa D2 ho fumaneha ha li-receptor le ho itaola, re khothalelitse hore litšoene tse ka tlaasana li ka itaola k'hok'heine ho feta litšoene tse hlaheletseng. Khopolo-taba ea rona e ile ea etsoa (Morgan et al a. 2002). Ebile, cocaine e ne e se se matlafatsang ho litšoene tse hlahelletseng ha e ne e hlahlojoa tlasa kemiso ea FR 50 ea matlafatso (bona Nader & Czoty 2005 bakeng sa lipuisano tse ling).

Re boetse re ile ra hlahloba boitsoaro bo bong boo re bo khethileng e ka ba mekhoa e fapaneng e khethollang maemo sechabeng. Thutong ea rona ea pele (Morgan et al a. 2000), ts'ebetso ea locomotor e boletseng esale pele boemo ba maemo a bophelo sechabeng seo litšoene tse ka tlaasana tsa maemo a tlase li ne li na le lintlha tse phahameng haholo ha li bapisoa le litšoene tse hlahelletseng; Ho khahlisang, sena ha sea ka sa fetisetsoa ho litšoene tse tšehali (Riddick et al a. e romelletsoe). Haufinyane tjena, re atolositse mehato ea rona ho kenyelletsa boits'oaro bo nkoang ho lekola ho se ts'oanehe ka boiteko ba ho atolosa mosebetsi oa morao-rao ka litoeba (mohlala. Perry et al a. 2005; Dalley et al a. 2007). Sehlopheng sa litšoene tsa basali tsa cynomolgus tse lekang ka kotloloho, re sebelisitse mokhoa o mong oa ho ngola ntho e le 'ngoe le e' ngoe pele re ka kenella pusong ea batho ba bang (Riddick et al a. e romelletsoe). Litšoene tse neng li tla qetella li le maemong a tlase li ne li khuts'oane ho ea fihla ho ntho e ncha ha li bapisoa le litšoene tse tšehali tse hlahelletseng. Bokhutšoane bo bokhuts'oane bo hloahloa ho emela ho kenella ho ho feta. Hore na litšoene tse kenang ka bongata le tsona li kotsing ea ho itšebeletsa koae joalo ka ha ho tlalehiloe litlalehong Perry et al a. (2005) 'me Dalley et al a. (2007) e ntse e hlahlojoa hona joale.

(ii) Likamano tsa tikoloho le tikoloho: karolo ea 2

Mo metsong ea rona ea litšoene tse tšehali, re ekellelitse mosebetsi oa pejana ho leka ho ntlafatsa mohlala oa maemo a batho. Liteko tsena li shebile haholo ka ho fetola maemo a tikoloho. Mohlala, re fumane hore tšusumetso e sirelletsang e amanang le ho ba tšoelesa ea tonanahali e ka lemohuoa ka ho pepesehela cocaine (Czoty et al a. 2004). Ka mantsoe a mang, ha ho ne ho e-na le phapang ea litekanyetso tsa ho itaola ha qalong ho pepesoa lenaneong la FR 50 (Morgan et al a. 2002), ho pepesetsoa khafetsa cocaine ka nako ea lilemo tsa 1 ho ile ha etsa hore koae e fetohe e matlafatsang litšoene tse hlaheletseng (sheba mohlala. Setšoantšo sa 2a). Kamora ho qeta likhoeli tse 'maloa ho isa lilemo tsa ho itaola, ho sa natsoe sekhahla sa karabelo kapa D2 fumaneha ka li-receptor li ne li fapane haholo ha li bapisoa le litšoene tse tlasa maemo a tlase (Czoty et al a. 2004). Joalokaha ho boletsoe kaholimo, li-schedule tse bonolo ha li fane ka tlhahisoleseling e amanang le matla a ho matlafatsa. Kahoo, re ile ra hlahloba hore na ho na le phapang pakeng tsa maemo a sechaba tlas'a maemo ao ho 'ona k'hok'heine e neng e fumaneha maemong a mofuta o mong, o sa khothalletseng lithethefatsi (Czoty et al a. 2005). Re fumane hore litšoene tse tlasa maemo a tlase li ne li ameha ka ho teba ka litlamorao tse matlafatsang tsa koae e sebelisang mokhoa ona, e le hore ba ka khetha tekanyetso e tlase ea cocaine holim'a lijo ha e bapisoa le litšoene tse hlaheletseng (Setšoantšo sa 2b). Liphumano tsena li bonts'a likarolo tse 'maloa tsa bohlokoa tsa tšebelisano ea manyolo le tikoloho. Lintlha tsena li ts'ehetsa maikutlo a hore mehato ea ho matlafatsa matla e fana ka tlhaiso-leseling e fapaneng e amanang le ho itaola ka koae ho feta mehato ea ho matlafatsa. Ntle le moo, liphumano tsena li bonts'a hore kamora lilemo tsa ho phela ka har'a lihlopha tsena tse tsitsitseng tšusumetso ea maemo a sechaba e ne e ntse e bonahala.

Setšoantšo sa 2 

(a) K'holeseterole ea Cocaine - karabelo ea mothapo o moholo oa monna (C-5386). Li-circuits tse tlatsitsoeng (tsa mantlha) li nkuoe nakoana kamora hore lits'ebetso tsa boiketlo ba sechaba li tsitse (li fetoloe ho tloha Morgan et al a. 2002); Li-circuits tse bulehileng ke karabo e khethiloeng hape ea koae ...

Potso e botsoang khafetsa ke hore 'ho thoe'ng haeba maemo a fetoha' me litšoene tse hlahelletseng li fetoha tse tlaasana ebe tšoene e honyenyane e fetoha e phahameng? ' Ho araba potso ena, re ile ra hlophisa lihlopha tse tšoanang le hore pene e le 'ngoe e ne e e-na le litšoene tse' ne tse hlaheletseng (tsa maemo a pele) mme pene e 'ngoe e ne e entsoe ke litšoene tse' ne tsa pele (tsa maemo a bone) tse fetileng. Lipeni tse ling li ne li entsoe ka litšoene tse mahareng (oa bobeli le oa boraro) le litšoene tse tsamaeang ka mokhoa o itekanetseng (Czoty et al a. ka ho itukisetsa). Kamora likhoeli tse tharo tsa matlo a boiketlo ba batho tlasa maemo ana a macha, lithuto tsa PET li ile tsa etsoa mme tsamaiso ea boikoetliso ea koae e ile ea hlahlojoa tlasa kemiso e tšoanang ea ho matlafatsa le lijo e le mokhoa o mong. Kamano pakeng tsa maemo a macha a bophelo le D2 ho fumaneha ha li-receptor ho ne ho sa bonahale - ke hore, litšoene tse neng li sa tsoa busa li ne li se na maemo a phahameng haholo a D2 phihlello ea receptor ha e bapisoa le litšoene tse sa tsoa feta. (Hlokomela, tse ling tsa litšoene tse tummeng li ne li le kaholimo ho tse ling 'me litšoene tse ling tse ikokobelletsang li kile tsa ba matla.) Hape, ho ne ho se na phapang ea khetho ea koae pakeng tsa litšoene. Boithuto bo eketsehileng bo sebelisang mehato e meng, ho kenyelletsa ho nchafatsoa hoa ntho, ba hlokometse hore boemo ba pejana bo ne bo rere sephetho ho feta boemo ba hona joale. Ho na le lingoliloeng tse telele le tse pharalletseng tse mabapi le boitšoaro le nalane ea litlhare tse susumetsang boitšoaro le litlamorao tsa lithethefatsi (mohlala Barrett et al a. 1989) mme lithuto tsena li holisa liphumano tseo ho kenyelletsa nalane ea lipuisano tsa sechaba.

Mohlala o mong oa tšebelisano ea tikoloho ea litho tsa 'mele o kenyelletsa tšebeliso ea litšoene tse bolokiloeng sechabeng ho lekola liphetoho tse tlisoang ke lithethefatsi lithutong tsa sechaba le sephetho sa litlamorao tsa ho itšireletsa ha koae. Ho na le lingoliloeng tse pharalletseng mabapi le tšebelisano ea maemo a sechaba le litlamorao tsa lithethefatsi lithutong tse seng tsa batho (mohlala Smith le Byrd 1985; Martin et al a. 1990; e hlahlojoe ke Miczek et al a. 2004). Mohlala, Miczek le basebetsi mmoho (mohlala Miczek & Yoshimura 1982; Miczek & Khauta 1983a) li bontšitse hore litlamorao tsa joala, amphetamine kapa cocaine li ka susumetsoa ke maemo a sechaba le tikoloho. Phuputsong e le 'ngoe (Winslow & Miczek 1985), tlase ho isa ho bohareng litekanyetso tsa joala tse hlahisoang li eketseha ka mabifi ke litšoene tse hlahelletseng, empa ha li na phello ea mabifi ke liphoofolo tse tlasa lefatše. Leha ho le joalo, tsamaiso ea tšebelisano ea joala le testosterone ho hatella litšoene e felletse ka hore ho be le qhoebeshano e ngata. Crowley et al a. (1974, 1992) a hlahloba litlamorao tsa lithethefatsi tse 'maloa tse hlekefelitsoeng ho boitšoaro ba macaques. Methamphetamine e hlahisitse keketseho e potlakileng ea maikutlo le lits'oants'o tse mpe, mme ea fokotseha mokhoeng o khothalletsang lijo le mabifi. Mohlapeng oa boemo bo tlaase-tlase, litekanyetso tse phahameng tsa methamphetamine li hlahisitse keketseho e kholo boits'oarong bo ikokobelitseng hoo palo ea mabifi e lebisitsoeng ho tsoa ho (e sa buuoang) litšoene tse matla ho phoofolo e tšoaroang ka lithethefatsi e eketsehile. Ho liphuputso tsohle tse hlahlobang litlamorao tsa lithethefatsi mabapi le boitšoaro ba sechaba, sephetho sena ke e 'ngoe ea litlhaloso tse fokolang tsa boits'oaro ba litšoene tse sa phekoloang. Ho litšoene tsa rona tse nang le botsoalle sechabeng, re ile ra leka polelo ea hore haeba ho matlafatsa tekanyetso ea koae ho ka baka mabifi le liphetoho tse teng maemong a maemo a bophelo, joale khafetsa boits'oaro ba koae ho monkey eo bo tla eketseha litekong tse latelang tsa liteko.

Litšoene li ne li phela ka lihlopha tse tsitsitseng tsa maemo a boiketlo ba sechaba mme maemo a sechaba a ne a behiloe ka pene e 'ngoe le e' ngoe joalokaha ho hlalositsoe ka holimo. Bakeng sa lithuto tsena, ke monkey e le 'ngoe feela sehlopheng sa maemo a bophelo e fuoeng monyetla oa ho sebelisa koae (letsoai, 0.01-0.1mgkg-1ente-1) tlasa kemiso ea FR 50 ea ntlafatso, ha litšoene tse setseng ka penseng li ne li khona ho hlahisa tlhahiso ea lijo tlasa kemiso ea FR 50; maemo a ile a lula a ntse a sebetsa ka linako tse hlano tse latellanang. Ha seboka se phetheloa, litšoene li ile tsa khutlisetsoa mekhatlong ea tsona ea boithabiso le boits'oaro bo ikokobelitseng bo tlalehiloeng ka 15nako ea metsotso. Litšoene tsohle (tse matla, tse bohareng le tse tlase) li ne li ithutoa litekong tsohle tsa koae. Litšebelisano tsa sechaba ha lia ka tsa ama litekanyetso tsa karabelo kapa ho ja koae bakeng sa monkey efe kapa efe. Le ha ho le joalo, liphetoho tse susumetsoang ke koae ka ts'ebeliso ea koae li ne li itšetlehile ka boemo ba monkey. Ho sa tsotelehe hore na ke phoofolo efe ka pitseng e ipehang, ke litšoene tse boemong ba pele le tsa bobeli li bontšitseng keketseho e mabifi; monkey e nyane ha e e-so ka e bonts'a mabifi nakong ea thuto. Lintlha tsena li bonts'a hore maemo a sechaba ke sesupo sa liphetoho tsa bohloka tse khothalletsoang ke koae. Lebaka le leng le ka 'nang la bakoa ke hore boithati bo ne bo sa ananele litlamorao tsa boitšoaro ba sechaba ke hore phihlello ea koae e ne e sa hlophisetsoa ho fihlela lihora tse ka bang 24 kamora puisano ea sechaba. Boithuto ba hajoale bo hlahloba litlamorao tsa liphetoho tse susumetsoang ke koae ka ts'ebetso ea boithabiso e amanang haufi le nako.

2. Liphello

Morero oa tlhahlobo ena e ne e le ho totobatsa lintlha tse 'maloa tsa bohlokoa tse sebelisang tšebeliso e mpe ea lithethefatsi ho sebelisa mehlala ea liphoofolo. Mefuta eohle ea liphoofolo, joalo ka bonyane, e no rerela pheletso e itseng ea kliniki. Mefuta ea liphoofolo ea ho itaola lithethefatsi mohlomong ke mohlala oa phoofolo o tšepahalang ka ho fetisisa oa boemo ba motho bo fumanehang ho bafuputsi (bona Griffiths et al a. 1980). Ha ho kenyeletsoa boitšoaro ba batho bao e seng batho le lithethefatsi tsa koae, mehlala ena ke mehlala ea tlhekefetso ea batho ea lithethefatsi. Re hlalositse lithuto tse entseng lipatlisiso tsa boitšoaro le li-neuropharmacological tse fumanoeng e le litšobotsi tse fetotsoeng mo maemong a tlokotsing. Re boetse re hlalositse maemo ao ho 'ona maemo a sechaba le a tikoloho a hlahisitseng liphetoho tse eketsang kapa ho fokotsa tlokotsi ea tlhekefetso ea lithethefatsi.

Ha ba nahana ka mehlala ea bokhoba ba lithethefatsi, bafuputsi ba tsepamisitse maikutlo lintlheng tse ka eketsang kapa tsa fokotsa taolo ea lithethefatsi. Mohlala, re tsebile ka nako e telele hore khatello ea maikutlo e ka eketsa tlokotsi ea ho ithaopela ho sebelisa koae. Mohlomong ntho ea bohlokoa haholo ke kutloisiso ea hore ho ruisa tikoloho ho ka hlahisa melemo ea matla ea lithethefatsi. Ha ho bontšoe feela hore batho ba bang ba sa ntlafatsoeng ke lithethefatsi ntle le lithethefatsi ba ka fokotsa tlokotsi (Carroll et al a. 1989) le tlhokomelo ea boits'oaro ba cocaine (Nader & Woolverton 1991, 1992), empa boiphihlelo bona ka lihokelo tse ling tse fapaneng, tseo hangata ho thoeng ke ntlafatso ea tikoloho, li ka fokotsa matlafatso ea koae. E le mohlala oa ho qetela oa tlhahlobo ena, re totobatsa lithuto tse peli tsa pele tse ileng tsa tlaleha litlamorao tse matla mabapi le ho matlafatsoa ha koae ho litšoene tse bolokiloeng sechabeng. Matšoenyeho a maholo, a ho kenella ka pene ea litšoene tse ling (bona Miczek & Khauta 1983b; Miczek & Tidey 1989) e ka ama matla a matlafatsang a cocaine. Le ha tlhaiso-leseling e le ea pele, ho bonahala eka litlamorao tsa ho ba motho ea kenang mokhatlong o hlophisitsoeng oa sechaba li fapane ho latela maemo a motho ea kenang. Ha tšoene e tlaasana e kenella pene e tiisitsoeng hantle ea litšoene tse tona tse 'nè tse nang le batho sechabeng, mothinya oa phoofolo ea "cocaine" - o ka fetoha ka letsohong le letšehali, ha ts'ebeliso e ts'oanang ea senokoane le tšoene e hlahelletseng e ka baka liphetoho tse nepahetseng. karolong ea karabelo ea lethal dose-cocaine. Ka lehlakoreng le leng la ts'ebetso, ho beha litšoene (ho sa tsotelehe maemo a sechaba) ka masakeng a maholoanyane a nang le lintho tse ncha matsatsing a 3 pele ho ho ithuta ho itaola ho felletse ka ho fetoha ka ho le letona mohalong oa karabelo ea cocaine, joalo ka litekanyetso e khethiloeng ho feta lijo pele boemo ba nontšo e ne e se e sa matlafatse. Liphuputso tsena li fana ka maikutlo a hore monono oa tikoloho, esita le litšoene tse pepeselitsoeng khatello ea maikutlo e sa foleng, joalo ka liphoofolo tse tlase, li ka hlahisa litlamorao tse matla menyetla ea ho itaola. Liphuputso tsena li tsamaellana le lithuto tsa batho tse bontšang hore mefuta e meng ea matlafatso le ntlafatso ea tikoloho e ka eketsa nako ea ho ila koae (Higgins 1997). Patlisiso e hlalositsoeng tlhahlobisong ena e bontšitse khafetsa hore tikoloho e ka ba le litlamorao tse matla tšebeliso ea lithethefatsi le hore ho na le liphetoho tsa neurobiological tse tsamaeang le litlamorao tsena. Re lumela hore motsoako oa ntlafatso ea tikoloho le pharmacotherapy o tla sebetsa hantle ho phekola bokhoba ba koae.

lumela hore baa fokola

Liphetoho tsohle tse entsoeng ka liteko tse hlalositsoeng tlhahlobisong ena li entsoe ho latela Lekhotla la Naha la Lipatlisiso Tataiso bakeng sa Tlhokomelo le Ts'ebeliso ea Limmammali ho Neuroscience le Behahlangual Research mme ba amoheloa ke Komiti ea Tlhokomelo ea Liphoofolo le Ts'ebeliso ea Yunivesithi ea Wake Forest. Tlatsetso ea tikoloho e ile ea fanoa joalo ka ha ho hlalositsoe Lenaneong la Tlhokomelo ea Liphoofolo le Ts'ebeliso ea Univesithi ea Tsoha ea Tlhaho ea Batho ba Tikoloho e seng Batho.

Re leboha KA Grant, LJ Porrino, RH Mach, JR Kaplan le HD Gage ka tšebelisano-'meho ea bona ea nako e telele le liphallelo ho etsa lipatlisiso tsena le ho Susan Nader, Tonya Calhoun, Mikki Sandridge, Michelle Icenhower le Nicholas Garrett bakeng sa thuso ea bona e ntle ea theknoloji ho tsena tsohle merero ea lipatlisiso. Patlisiso e tsoang laboratoring ea rona le ho lokisa buka ena e ne e tšehelitsoe karolo ea NIDA lithuso DA 10584, DA 017763, DA 14637 le DA 06634.

Mongolo o botlaaseng ba leqephe

Tlatsetso e le 'ngoe ea 17 Tlatsong ea Seboka sa Puisano' Mokhoa oa ho ba le bothata ba ho lemala: lits'ebeletso tse ncha '.

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