Neuropsychopharmacology (2007) 32, 1678-1686; doi: 10.1038 / sj.npp.1301295; e phatlalalitsoeng marang-rang 3 ka January 2007, Martin Zack1,2,3 le Constantine X Poulos4, Tokomane: Ngaka M Zack, Clinical Neuroscience Karolo, Setsi sa Tlatsetso le Bophelo ba Kelello, 33 Russell Street, Toronto, ON, Canada M5S 2S1.
HO HLOKA
Patlisiso e fetileng e bontšitse likarolo tse arolelanoang tsa "neurochemical" bakeng sa papali ea papali ea chelete le psychostimulant. Sena se fana ka maikutlo a hore li-suboprates tsa dopamine li ka laola ka kotloloho ts'ebetso ea ho matlafatsa ho papali ea papali ea methapo.
Ho etsa lipatlisiso mabapi le bothata bona, boithuto ba hona joale bo lekotse litlamorao tsa mohanyetsi oa dopamine ea D2 ea khethiloeng, haloperidol (3 mg, molomo) ho likarabo ho papali ea 'nete ea ho becha (15 min ka mochini oa slot) ho 20 bao e seng comorbid pathological gambler and 18 non- taolo ea papali ea chelete ea ho becha ka mokhoa o laoloang ke placebo, o foufetseng habeli, le boqapi bo hanyetsanang.
Ho papali ea papali ea chelete, haloperidol e eketsehile haholo litlamorao tse tlalehiloeng tse monate tsa papali ea papali ea chelete, papali ea papali ea papali ea papali ea papali ea papali ea chelete le papali ea chelete ea papali ea chelete. khatello ea mali, empa ha e na phello ho li-indices tse ling. Liphumano li fana ka bopaki bo tobileng ba liteko tsa hore D2 substrate e matlafatsa ho matlafatsoa ha papali ea papali ea chelete.
Keywords:
papali ea chelete, dopamine, D2, haloperidol, moputso, priming
SELELEKELA
Ho becha ka tsela ea tlhaho ke bokuli ba kelello boo hangata bo ka bakang litlamorao tse mpe (Morasco et al, 2006; Scherrer et al, 2005). Bopaki ba marangrang a methapo ea methapo ea meputso e khothatsang kapa e matlafatsang ea ts'ebetso ea papali ea chelete ka boeona e se e qalile ho hlaha. Phuputso ea morao-rao ea fMRI e fumane hore papali ea papali ea papali ea chelete e kang ho becha e nang le meputso ea chelete e kenya tšebetsong sistimi ea moputso oa mesolimbic ho batho ba papali ea papali ea chelete le taolo (Reu ter et al, 2005). Phuputso ena e fumane hore ts'ebetso ea mesolimbic e hlohlellelitsoeng ke papali e ne e le tlase ho bapapali ba papali ea chelete ho feta taolo, 'me ha lefu la papali ea chelete le le matla le ho feta, ts'ebetso ea ts'ebetso ea papali e fokola. Bafuputsi ba ile ba toloka seo ba se fumaneng e le se lumellanang le 'lefu la khaello ea moputso' bathong ba papali ea chelete.
Mosebetsi o mong o fumane hore ho kenella ka har'a casino ea nnete papali ea chelete e phahamisa tšebetso ea "hypothalamic-pituitary axis" e leng bothata le ho becha ho seng bothata, joalo ka ha ho bonts'oa maemo a eketsehang a plasma a norepinephrine, cortisol, le keketseho e lekanang ea sekhahla sa pelo (Meyer et al, 2004). Ntle le moo, papali ea papali ea casino e ile ea lebisa maemong a phahameng a dopamine ka lihlopha tsena ka bobeli, 'me maemo a holimo a hlaha lihlopheng tsa papali ea chelete.
Morero o mong oa ho botsa o sebelisitse leano la priming la pharmacological ho hlakisa li-mediochemical general mediers tsa ho matlafatsa papali ea chelete (Zack le Poulos, 2004). Phuputso ena e fumane hore nonspecific dopamine agonist, d-amphetamine, ka mokhoa o ikhethileng o susumetsa tšusumetso ea ho becha ho becha ha basekaseki. Ho fumana hona ho bonts'a likarolo tse arolelanoang tsa "neurochemical" tsa ho becha le moputso oa psychostimulant. Sena se fana ka maikutlo a hore, joalo ka maemong a li-psychostimulants, ts'ebetso ea likaroloana tse ikhethileng tsa dopamine e ka laola ka kotloloho ts'ebetso ea matlafatso ho papali ea chelete. Bopaki ba taba ena bo bohlokoa bakeng sa ho utloisisa litlamorao tse tšoanang le tsa papali ea chelete ho batho ba tlokotsing.
Patlisiso e kholo e khannetse receptor ea D2 e le moputso oa bohlokoa oa substrate modulating psychostimulant (Nader le Czoty, 2005; Self and Stein, 1992; Volkow et al, 1999, 2002). Ntle le moo, lipatlisiso mabapi le ho ba kotsing ea ho becha ha methapo ea methapo ea methapo li hatisitse bohlokoa ba receptor ea D2 kotsing ea liphatsa tsa lefutso ena (Comings et al, 1996). Sena se tsamaisana le lipatlisiso tse ling tse bonts'ang khokahano e matla lipakeng tsa anomalies liphatseng tseo khoutu ea li-receptor ea D2 e leng kotsing ea likotsi tse fapaneng tsa tlatsetso (Blum et al, 1995, 1996).
Lithuto tse nang le phetoho e fumanehang khafetsa ho D2 binding receptor (ke hore, phumaneho e tlase) ho batho ba bonts'ang mathata a tlatselletsang a khothalletsang, ho kenyeletsa le tlhekefetso ea koae le methamphetamine (Volkow et al, 1990, 2001), bokhoba ba tahi ea heroin (Wang et al, 1997), bokhoba ba tahi. (Volkow et al, 1996), le botenya (Wang et al, 2001).
Mokhoa ona oa sephetho o khothalelitse tšusumetso ea hore ho batla ho matlafatsang ha litlatsetso ho ka emela karabelo e tlatselletsang ho bofokoli ba lipakeng kapa tsa lithethefatsi mosebetsing oa D2 receptor function (mohlala Mohau, 2000; Noble, 2000; Volkow et al, 2004).
Tumellanong le sena, lino tse tahang tse nang le li-receptor tse tlase tsa D2 li tlaleha ho labalabela ho eketsehileng 'me li bonts'a ts'ebetso e kholo ea ts'usumetso ea cortex ea medial pele ho pele le cingate ea ka ntle-likarolo tsa boko tse kenyellelitsoeng moqoqong le tlhokomelong (Heinz et al, 2004). Ho batho ba lemaletseng koae, lipatlisiso tsa PET li bonts'a hore ho pepesetsoa hoa cocaine cueine ho eketsa ts'ebetso ea dopamine ea endo native ho D2 receptors ho dorsal striatum le boholo ba phello ena bo bolela ho lakatsa (Volkow et al, 2006). Liphumano tsena li fana ka maikutlo a hore batho ba nang le li-receptor tse tlase tsa D2 ba kotsing ea ho susumetsoa ke tšusumetso ea moea o matla le hore maemo a phahameng a phetisetso ea dopamine li-receptor tsena a ka kenella ts'ebetsong ena ka kotloloho.
Ka lebaka la bopaki bona mabapi le bohlokoa ba receptor ea D2 bothateng ba papali ea chelete le mathata a mang a ho lemalla, thuto e teng hona joale e ile ea hlahloba litlamorao tsa mohanyetsi ea ikhethileng oa D2, haloperidol mabapi le likarabo khaolong e khutšoanyane ea motjeko oa slot oa papali ea papali ea chelete le lits'ebetsong tse nepahetseng tsa taolo ea papali ea chelete. .
LISEBELISOA LE MEKHOA
Litšobotsi tsa Sehlooho
Batho ba mashome a mabeli (ba bararo) ba basali ba sa sebetsanang le kalafo ba batlang papali ea chelete, ba sa tšoaroe ke letho litekong tsa tlhatlhobo, mme 18 (basali ba bane) ba laola bophelo bo botle, ba ile ba hiroa ke lipapatso tsa likoranta mme ba lefelloa ho nka karolo. Ba bechang ba ile ba eletsoa ka ho hlaka hore thuto e ne e sa reretsoe ho sebetsana le mathata a bona a papali ea chelete. Lihlooho tsohle li ile tsa hlahlojoa ke ngaka pele li hlahlojoa. Lilemo tsa mohlala e ne e le 21-64 (M = 38.9, SD = 11.7) lilemo. Ho ne ho se na liphapang tsa sehlopha ho mefuta efe kapa efe ea palo ea batho. Ha ho sehlopha se bontšitseng maemo a phahameng a bongaka ka ho tšoenyeha, khatello ea maikutlo; tšebeliso ea joala kapa tšebeliso e mpe ea lithethefatsi. Li-drink (SD) tsa beke / beke e ne e le 2.8 (2.4) bakeng sa batho ba becha le 1.6 (1.9) bakeng sa taolo. Maemo a bolelang (SD) ho foromo e khuts'oane ea Beck Depression Inventory (Beck le Beck, 1972) e ne e le 3.6 (3.1) bakeng sa batho ba bechang, le 1.1 (1.9) bakeng sa taolo.
Bacha bohle ba papali ea papali ea chelete ba fumane 5 (M = 11.0, SD = 4.4) bakeng sa papali ea papali ea bongaka ea DSM-IV (Beaudoin le Cox, 1999). Litšenyehelo tsa bona tsa papali ea chelete li ne li le ngata. Litsenyehelo tsa beke le beke tsa mean (SD) ho becha e ne e le $ 279 (266), e tsamaellanang le 20.3% (12.4) ea moputso oa bona, ka tahlehelo e phahameng e fumanehang ketsahalong e le 'ngoe ea $ 7563 (22 179). Botsamaisi bohle ba fuoe 0 ho DSM-IV, ba qetile $ 1.0 (1.3) ka beke ho becha, mme ba tlaleha tahlehelo e phahameng e fumanehang ka nako e le 'ngoe ea $ 7.1 (8.4). Kahoo, ha e le hantle batsamaisi e ne e se batho ba bechang. Har'a ba bechang, mesebetsi ea kamehla ea papali ea chelete ea ho becha e ne e le: lipapali tsa casino (15 / 20), lits'oantso (12 / 20), lipapali (8 / 20), li-horseracing (6 / 20), lottery (4 / 20), le bingo (1 / 20 ).
Sekala le Lisebelisoa
Sekala sa "analog" se bonoang (VAS; 0-10; Ha ho joalo ka ho fetesisa) se lekantsoeng le liphello tse ntle tsa "capule". Setsi sa Tlhatlhobo ea Litaba tsa Tlatsetso (ARCI; Haertzen, 1965) se fane ka tekanyo e lekantsoeng ea litlamorao tsa litla-morao tsa lithethefatsi, le mofuta o mokhuts'oane oa Profil of Mood States (POMS; Shacham, 1983) o lekantseng mefuta e fapaneng ea linaha.
VAS e boetse e lekantse litlamorao tse khahlisang (Ho natefeloa, ho hlasimoloha, ho kenyelletsa) papali ea slot mochini, hammoho le Desire to Gamble.
Mosebetsi oa ho bala ka potlako (Lexical Salience Task) o lekantse nako ea karabelo ea ho bala (ka ms) ho mantsoe a litšila a Ho becha (mohlala w * a * g * e * r) le mantsoe a Neutral (mohlala w * i * n * d * o * w) . Mosebetsi le sepheo sa tsona li ts'oana le tse hlalositsoeng thutong e fetileng (Zack le Poulos, 2004). Salience e hlalosoa ka mokhoa o fapaneng e le phapano ea ho bala latency ho Gossip vs mantsoe a se nang 'nete.
Mochini oa thekiso ea khoebo o sebelisoang hajoale likasinong tsa Ontario ('Cash Crop'; WMS Gaming Inc., Chicago, IL) e sebelitse joalo ka hlooho ea khothatso. Bafo ba ne ba ka becha mokitlane oa 1–45 / spin, 'me ba bolelloa hore ba tla fumana chelete ea bonase e lekanang le palo ea bona ea hoqetela ea mokoloto lenaneong ka leng.
Khatello ea mali e ile ea hlahlojoa ka automate wrist cuff (HEM-601 Omron Inc, Vernon Hills, IL).
Khetho ea Haloperidol e le Dopamine D2 Probe
Haloperidol (3 mg, molomo) e kenya sebaka sa 60-70% D2 receptor mme e fihla sehlohlolong sa mali ho 2.75 h kamora tsamaiso (Nordstrom et al, 1992). Ho bahanyetsi ba dopamine ba fumanehang bakeng sa ts'ebeliso ea batho Canada, haloperidol (haholoholo tekanyong e tlase ea bongaka e sebelisitsoeng phuputsong ena) ke eona e khethang mokelikeli oa D2 haholo. Lintlha tsa in vitro tse tsoang likhoto le lisele tsa motho tse entsoeng ka letsoho (Arndt le Skarsfeldt, 1998; Schotte et al, 1996) li bonts'a kamano ea haloperidol bakeng sa D2 e feta makhetlo a 15 ho feta D3, e amohelang dopamine eo e nang le kamano e latelang e kholo; 9-13 makhetlo a maholo ho feta bakeng sa -1 adrenoreceptor; le makhetlo a 18-34 a maholo ho feta seamoheli sa serotonin 2A; ntle le kamano e ntle ea libaka tse ling tse tlamang. Liphuputso tsa boko ba motho kamora lefu la lefu (Richelson le Souder, 2000) li bonts'a kamano e nyane ea -1 adrenoreceptor (15% ea kamano ea D2). Ntho e ikhethang ho boemo bona bo ikhethileng bo tlamang ke sigma receptor, eo haloperidol e tlamang ka kamano e batlang e lekana le ea receptor ea D2 (Schotte et al, 1996). Sena se ka tlatsetsa ho bokhoni ba eona ba ho felisa lipono (bapisa le Keats le Telford, 1964).
Tsamaiso
Boithuto bona bo ile ba etsoa tumellanong le litekanyetso tsa boitšoaro tsa Polelo ea Helsinki (1975). Kamora ho fana ka tumello e nang le tsebo, lithuto li bile teng libokeng tse peli tsa liteko, 1 beke ka thoko (ho netefatsa ho hlatsuoa), moo ba fumaneng 3 mg molomo haloperidol kapa placebo ka moralo o sa boneng mahlo, o hanyetsanang.
Sebokeng se seng le se seng sa liteko, 2.75 h ka mor'a ho qeta dosing, lithuto li ne li bapala mochini oa slot o nang le $ 200 ka litefiso ka laboratoring ea mock-bar. Ba ile ba becha bakeng sa metsotso ea 15 kapa ho fihlela mekoloto ea bona e felile.
ARCI le POMS li ne li tsamaisoa ka pele ho khubung, hape hape kapele pele ho papali ea slot Machine maemong a litekanyetso tsa lithethefatsi tsa mali a lebelletsoeng. Takatso ea Gamble e ile ea lekisoa ka makhetlo ana a mabeli le hantle kamora papali ea slot Machine. Litholoana tse khahlisang li ile tsa lekanngoa kamora papali ea slot mochini e lateloang hanghang ke Lexical Salience Task. Khatello ea mali e lekantsoe le linako tsa 30-min nako eohle.
Ho fokotsa litlamorao tse ka hlahang tsa mochini oa slot, lithuto li ile tsa sala li le laboratoring ea 4 h kamora hore tlhahlobo e phethoe. Ba ile ba hlahlojoa ke mooki ea ngolisitsoeng pele ba lelekoa 'me ba romeloa hae ka tekesi e sa lefelloeng. Ha a qeta ho lelekoa, lithuto li ile tsa fumana tekanyetso e tiisitsoeng ea 50-mg ea diphenhydramine (Benadryl) hore e sebelisoe ketsahalong e liehang ea ho fetoha.
Mokhoa oa Tlhahlobo ea Tlhahlobo
Litlamorao tse bolelang li ile tsa hlahlojoa ka 2 (Kalafo: Lithethefatsi, Placebo) 2 (Sehlopha: papali ea chelete, lits'oants'o) litlhahlobo tsa phapang (ANOVA). Moo ho loketseng, mefuta-futa ea lihlooho-tsa litaba e kenyelelitsoe ho ANOVA (mohlala boemo ba lentsoe ho Lexical Salience Task). Bakeng sa mefuta-futa moo lintlha tsa mantlha tsa pre-capsule li neng li fumaneha (lintlha tsa VAS tsa Desire to Gamble), litlhahlobo tsa covariance (ANCOVA) li ile tsa etsoa, ho sebelisoa lintlha tsa mantlha e le phapang, ho laola phapano ea liteko tse ling le ho arola litlamorao tsa kalafo (Wainer , 1991).
LIPOTSO
Liphello tsa Capsule
Ho lekola katleho ea ba sa boneng, qetellong ea lithuto ba ile ba botsoa ho tlaleha hore na ba lumela hore ba fumane moriana ka letsatsi lefe. A 2 (Tatellano ea Kalafo: Lithethefatsi Thutong ea 1, Lithethefatsi Thutong ea 2) 3 (Khetho ea Karabelo: Lumela Letsatsi la 1, Lumela Letsatsi la 2, Ha U Tsebe) 2 ea likarabo sampoleng e felletseng e ne e se ea bohlokoa, 2 (df = 2, N = 20) = 2.61, leq> 0.27. Ka kakaretso, lihlooho tse 33/38 li arabiloe 'Ha ke tsebe;' tse peli ka nepo le e 'ngoe e tlalehiloe ka phoso Seboka sa 1; le tse peli tse tlalehiloeng ka mokhoa o fosahetseng Karolo ea 2. Mohlala o ne o sa fapana ho bapalami ba papali ea chelete le taolo, 2 <2.3, p's> 0.32, ka tlaleho e le 'ngoe e nepahetseng ho batho ba papali ea papali ea chelete, le e' ngoe ho laola. Kahoo, bafo ba ne ba sitoa ho khetholla setlhare ho tsoa ho placebo, e le hore phapang efe kapa efe ea karabelo mochineng oa slot e ne e se ka lebaka la litlamorao tsa ho ba tlasa ts'usumetso ea setlhare ho matlafatsong ea papali ea chelete.
Lethathamo la 1 le bonts'a litlamorao tse boletsoeng ka boeona tsa SDLI, POMS, le VAS ho 2.75 h kamora ho thella (litekanyetso tse phahameng tsa lithethefatsi bakeng sa haloperidol) hammoho le lintlha tsa pre-capsule bakeng sa kalafo e ngoe le e ngoe ho tsa papali ea chelete le ho laoleng.
Tafole ea 1 - Mean (SD) Liphello tse Ikhethileng tsa Capsule (3 mg Haloperidol; Placebo) ho Peak Blood Levels (2.75 h Post-Administration) ka Sekala sa ARCI, POMS (foromo e khuts'oane), le Visual Analog Scales (Molemo / Liphello tse Mpe; 0-10) ho Lihlooho tsa Taolo e Phetseng Hantle (n = 18) le Papali ea papali ea chelete (n = 20).
ARCI
A 2 (Sehlopha) 2 (Phekolo) 2 (Nako) 7 (Sehlomathiso) ANOVA ea litekanyetso tsa ARCI e hlahisitse litlamorao tse latelang tse amanang le kalafo: Tšebelisano e bohlokoa ea Nako ea Phekolo, F (1, 216) = 5.50, p = 0.025, le a Tšebelisano ea nako e nyane ea kalafo ea nako ea kalafo, F (6, 216) = 2.06, p = 0.060, ntle le litlamorao tse ling tse amanang le Phekolo, p's> 0.50. Tšebelisano ea Nako ea Phekolo e bonts'itse phokotso e akaretsang ea lipalo ho tloha pre-capsule ho ea post-capsule tlasa haloperidol joalo ka khahlano le keketseho e akaretsang ea lipalo ho tloha ho pre-post-capsule tlasa placebo. Joalo ka ha ho bonts'itsoe ho Tafole ea 1, tšebelisano-'moho ea bohlokoa ea litsela tse tharo e bonts'itse phetoho e khethiloeng molemong oa lintlha tsa sekhahla sa MBG, se neng se tloaetse ho nyoloha ho tloha pele ho kamora 'capsule tlasa placebo ho bapapali ba papali ea chelete feela, empa ba fokotsehile ka bobeli lihlopha ho tloha pele ho poso-capsule tlasa haloperidol. Tataiso ea litlamorao le boholo ba litlamorao tsa li-Subscales tse fapaneng li tsamaisana hantle le lipatlisiso tse fetileng tse ileng tsa leka tekanyetso ea 3 mg ea haloperidol ho baithaopi ba phetseng hantle (Enggasser and de Wit, 2001; Wachtel et al, 2002). Phello ea mantlha ea Sehlopha, F (1, 36) = 5.46, p = 0.025, e bonts'itse lintlha tse batlang li phahame ka kakaretso (SD), tse kopantsoeng ho Subscales le Phekolo, ho batho ba papali ea chelete, 3.8 (0.8), ho feta taolo, 3.2 (0.8 ).
TSIETSI
A 2 (Sehlopha) 2 (Phekolo) 2 (Nako) 6 (Subscale) ANOVA ea litekanyetso tsa POMS ha ea hlahisa litlamorao tse amang Phekolo, p's> 0.10.
VAS
A 2 (Sehlopha) 2 (Phekolo) 2 (Subscale) ANOVA ea lintlha tsa VAS e hlahisitse tšebelisano e bohlokoa haholo ea kalafo ea kalafo, F (1, 36) = 3.44, p = 0.072, ntle le litlamorao tse ling tse amanang le kalafo, p's> 0.56 . Tafole 1 e senola hore sephetho sena se bonts'a keketseho e itekanetseng empa e tsitsitse ea litlamorao tse mpe tse tlalehiloeng sehlopheng ka seng tlasa haloperidol vs placebo, athe liphetho tsa Good Effects ha lia ka tsa fetoha ka kananelo ka lebaka la kalafo ea lithethefatsi.
Liphello tsa Slot Machine Game
Litlaleho tse monate tsa boithabiso
Setšoantšo sa 1 se bonts'a litekanyetso tsa SEM tsa boithabiso bo susumetsoang ke ho becha, Thabo le ho kenya letsoho mme e bonts'a hore haloperidol e eketse lintlha tse ngata sekhahla se seng le se seng sa batho ba papali ea chelete, empa ha ea ka ea bonahala e fetola lintlha ka kananelo ho taolo. Litemoso tsena li netefalitsoe ke litlhahlobo. A 2 (Sehlopha) 2 (Phekolo) 3 (Subscale) ANOVA e hlahisitse phello e kholo ea Sehlopha, F (1, 36) = 6.36, p = 0.016, tšebelisano ea sehlopha sa kalafo, F (1, 36) = 4.17, p = 0.048, 'me ha ho na litlamorao tse kholo tsa taolo, p's> 0.50. Phello ea Sehlopha e bonts'a lintlha tse phahameng ho bapapali ba papali ea chelete ho feta taolo ho Subscales le Phekolo. Tšebelisano e bonts'a keketseho e kholo ea lintlha tsa Subscale tlasa haloperidol ho batho ba bechang empa eseng ho taolo; 'Me ho haella ha litlamorao tse phahameng tsa taolo ho bonts'a hore haloperidol e bile le phello e ts'oanang ea keketseho ho li-subscales tsohle tse tharo. Phapang e arolelanoang e arolelanoang bakeng sa liphallelo tse tharo e ne e le r2 = 0.66, bakeng sa batho ba bechang, le r2 = 0.65, bakeng sa taolo. Kahoo, phello e tloaelehileng e khahlisang ea papali e bile karolo ea likarolo tse peli ho tse tharo tsa phapang lipapatsong tse nyane, athe hoo e ka bang karolo ea boraro ea phapang e ne e ikhethile ho sekala se seng le se seng.
Setšoantšo sa 1.
Mean (SEM) e itlaleha e le litlamorao tsa papali ea mochini oa slot oa metsotso e 15 lithutong tsa taolo e phetseng hantle (n = 18) le bapapali ba papali ea mafu (n = 20) tlasa haloperidol (3 mg, molomo) le placebo. * Phello ea kalafo ea lithethefatsi, p <0.001.
Boiteko ba ho itlhahisa ba ho becha
Setšoantšo sa 2 se bonts'a Thato (SEM) Takatso ea litekanyetso tsa Gamble pele le kamora papali ea slot. Palo e supa hore haloperidol ka boyona e ne e se na litlamorao ho Takatso ea pele ho papali sehlopheng ka seng. Lipalo tsa litakatso li phahame ho tloha pele ho papali tlasa playbo sehlopheng ka seng; mme tekanyo ea keketseho ena e susumetsoang ke papali e ile ea bonahala e le kholo haholo tlasa haloperidol ho ba bechang empa e se taolong. Ho sekaseka lintlha tsena.
Setšoantšo sa 2.
Bolela (SEM) takatso ea boithati ea ho becha pele le kamora papali ea mochini oa slot oa metsotso e 15 lithutong tsa taolo e phetseng hantle (n = 18) le bapapali ba papali ea mafu (n = 20) tlasa haloperidol (3 mg, molomo) le placebo. * Phello ea kalafo ea lithethefatsi, p <0.001.
2 ea pele (Sehlopha) 2 (Phekolo) ANOVA ea litekanyo tsa pre-capsule Desire (e sa bontšitsoeng) e hlahisitse phello e kholo ea Sehlopha, F (1, 36) = 38.39, p <0.001, 'me ha ho litlamorao tse ling, p's> 0.26, e bonts'ang takatso ea mantlha ea SD-pre-capsule ea takatso ea papali ea papali ea chelete, 3.6 (1.8) ho feta taolo, 0.4 (1.8) lenaneong ka leng la liteko. Ho arola kalafo ea kalafo (Wainer, 1991), 2 (Sehlopha) 2 (Phekolo) 2 (Pre-Post Game) ANCOVA ea Desire to Gamble scores e ile ea etsoa ho sebelisoa pre-capsule Desire scores joalo ka ha e fapana. ANCOVA e hlahisitse tšebelisano e kholo ea litsela tse tharo, F (1, 35) = 4.21, p = 0.048, le litlamorao tse ka sehlohlolong tsa Sehlopha, p = 0.056, e bonts'a lintlha tse phahameng ho bapalami ba papali ea chelete ho feta litsamaisong.
Liphuputso tse bonolo tsa litlamorao li fumane hore ho ne ho se na tšusumetso e kholo ea Phekolo takatsong ea papali ea papali bakeng sa ba bechang kapa taolo, p's> 0.50. Tlas'a placebo, papali e ile ea eketsa litakatso tsa takatso ho batho ba becha, t (35) = 6.31, p <0.001, le litsamaisong, t (35) = 3.90, p <0.001. Tlas'a haloperidol, keketseho ea pele ho poso ea Takatso e ile ea matlafatsoa haholo ho batho ba bechang, t (35) = 4.13, p <0.001, empa eseng taolong, p> 0.50. Kahoo, haloperidol e ile ea ntlafatsa litlamorao tsa papali ea mochini oa papali ho batho ba papali ea papali ea chelete.
Ts'ebetso ea marang-rang a semantic: mosebetsi oa ho nyehlisa ka mokhoa oa lexical
Lethathamo la 2 le tlaleha linako tsa karabelo ea ho bala (SD) ho bala (RT; ms) bakeng sa mantsoe a ho becha le a ho se lekane le maemo a mantsoe a Ancillary ho Lexical Salience Task bakeng sa taolo le baphethahatsi tlasa Kalafo e 'ngoe le e' ngoe. Lethathamo le bonts'a hore, sehlopheng ka seng, RT e ne e nyenyefatsa haholo mantsoe a se nang 'nete ho feta mefuta eohle e meng ea mantsoe tlasa placebo le haloperidol. Joalokaha ho hlokometsoe pejana, phapang ea RT ho sehlopha sa mantsoe a lebisitsoeng mabapi le mantsoe a sa sebetseng a Nutral a lekantsoeng a ho se sebetse hantle; le phapang e kholo, (Tarane ea ho se sebetse), e tla ba matla le ho feta.
Tafole ea 2 - Nako ea karabelo ea ho bala (S (SD) ea ho bala ea Word Stimuli ho Lexical Salience Task Under Placebo le Haloperidol (3 mg) ho Healthy Control Subjects (n = 18) le Pathological Gamblers (n = 20).
Tafole e feletseng
2 (Sehlopha) 2 (Phekolo) 5 (Boemo ba Lentsoe) ANOVA e hlahisitse tšebelisano e kholo ea litsela tse tharo, F (4, 144) = 3.00, p = 0.021. Liphuputso tse bonolo tsa litlamorao tsa taolo li fumane hore phapang ea RT ho tloha ho se nke lehlakore tlasa lithethefatsi vs placebo ha ea fetoha haholo bakeng sa mantsoe a papali ea chelete, p> 0.06; e eketsehile bakeng sa mantsoe a joala, t (144) = 7.50, p <0.001; 'me ea fokotseha bakeng sa tse peli tse ntle, t (144) = 7.91, p <0.001, le mantsoe a fosahetseng a amang maikutlo, t (144) = 11.08, p <0.001. Ka hona, litabeng tsa taolo, mantsoe a Papali ea chelete a ne a se bohlokoa ho feta lithethefatsi tlasa placebo; Mantsoe a joala a ne a le bohlokoa haholo tlasa sethethefatsi, mme mantsoe a amang maikutlo, ho sa tsotelehe valence, a ne a le tlase haholo tlasa sethethefatsi. Tlhahlobo ea lintlha tsa taolo ho Tafole ea 2 e bonts'a hore, tlasa placebo, RT ho mantsoe a Joala e ne e le butle butle ka mokhoa o sa tloaelehang ho latela mantsoe a mang a susumetsang. Kahoo, phapang e batlang e le kholo ho RT ho Alcohol vs mantsoe a sa jeleng paate tlasa haloperidol lithutong tsena e kanna eaba e bonts'itse khatello ea moelelo.
Ho hlahlojoa lintlha tsa RT bakeng sa batho ba bechang maemong a fapaneng a ho se nke lehlakore tlas'a li-placebo ho senola hore ka kakaretso li ne li tšoana. Liphuputso tse bonolo tse hlahisitsoeng ke papali ea chelete li fumane hore haloperidol e ekelitse phapang ea RT haholo ho tsoa ho Lehlakore bakeng sa mantsoe a papali ea chelete, t (108) = 2.91, p <0.01; le bakeng sa mantsoe a Ntle a Amang, t (108) = 5.26, p <0.001; empa ha a ka a fetola RT e amanang le mefuta e meng ea mantsoe, p's> 0.50. Kahoo, liphetho tsa papali ea chelete li bonts'a hore mantsoe a papali ea chelete le mantsoe a nepahetseng a ama li ne li le bohlokoa haholo tlasa haloperidol ho feta placebo.
Liphello tsa 'mele: khatello ea mali ea systolic
Setšoantšo sa 3 se bonts'a litlamorao tsa papali ea mochini oa slot ho khatello ea mali ea systolic (mmHg) tlasa haloperidol le placebo taolong. Setšoantšo sa 4 se bonts'a lintlha tse tsamaellanang bakeng sa ba bechang. Lipalo li supa hore, tlas'a placebo, khatello ea mali e eketsehile ho tloha papaling ea pele ho papali ka lihlopha tse peli. Ntle le moo, ka lihlopha tsena ka bobeli, keketseho e bakiloeng ke papali khatello ea mali e ne e le kholoanyane tlasa haloperidol. Maikutlo ana a netefalitsoe ke bohlahlobo.
Setšoantšo sa 3.
Def (SEM) khatello ea mali ea systolic (mm Hg) motheong oa pre-capsule le ka methapo ea 30 min le ka mor'a papali ea 15-min slot Machine lithutong tsa taolo e phetseng hantle (n = 18) tlasa haloperidol (3 mg, molomo) le placebo .
Sebopeho se felletseng le litšomo (15K)
Setšoantšo sa 4.
Def (SEM) khatello ea mali ea systolic (mm Hg) motheong oa pre-capsule le lipakeng tsa 30 min pele le kamora papali ea mochini oa 15-min slot ho marangrang a pathological (n = 20) tlasa haloperidol (3 mg, molomo) le placebo.
2 (Sehlopha) 2 (Phekolo) 8 (Nako ea Teko) ANOVA ea systolic khatello ea mali e hlahisitse tšebelisano e kholo ea Nako ea Phekolo, F (7, 252) = 2.64, p = 0.012, le tšebelisano e kholo ea litsela tse tharo, F (7, 252) = 2.89, p = 0.006. Tšebelisano-'moho ka litsela tse peli e bonts'a keketseho e sa fetoheng liphellong tsa Nako (kamora 'papali ho tlosoa bonyane ba papali) tlasa haloperidol vs placebo ho taolo, t (252) = 6.15, p <0.001, le ho batho ba bechang, t (252) = 5.16, le <0.001. Tšebelisano-'moho ea litsela tse tharo e bonts'itse phapang ea sehlopha ka nako eo bonyane ba papali ea pele bo etsahetseng tlasa kalafo e ngoe le e ngoe. Litaolo, khatello e tlase ea mali e etsahetse metsotso e 30 pele mochini oa slot o qala tlasa placebo mme hang pele ho papali tlasa haloperidol; ho batho ba bechang mokhoa ona o khutlisitsoe morao, mme bonyane ba papali ea papali bo etsahetse pele papali e qala tlasa placebo, empa metsotso e 30 pele papali e qala tlasa haloperidol Haholo-holo, haloperidol e ekelitse keketseho e bakiloeng ke papali ea khatello ea mali ho isa tekanyong e tšoanang lihlopheng ka bobeli. Boitšoaro ba ho becha papaling ea mochini oa slot Letoto la 2 2 ANOVA la boits'oaro ba papali papaling ea mochini oa sekotjana (ho bolela ho ts'oara likrediti ka spin, ho becha ho hoholo ka ho oela, mekitlane ea ho qetela e fumanoeng) ha ea hlahisa litlamorao tse amanang le Phekolo, p> 0.25. Sephetho se le seng sa bohlokoa e bile phello ea mantlha ea li-spins / papali ea li-mean (SD), tse neng li le ngata ho bapapali ba papali ea chelete, 89.4 (39.4) ho feta ho li-control, 60.6 (41.6), F (1, 36) = 9.57, p = 0.004.
TŠOHLOA
Haloperidol, ka boeona, e ne e se na litlamorao tse kholo litabeng tsa papali ea papali ea chelete le taolo e phetseng hantle litlamorao tse tlisoang ke lithethefatsi kapa litla-morao tsa maikutlo joalo ka ha ho hlahlojoa ke litekanyetso tsa lithethefatsi tsa ARCI, POMS le VAS. Lihlopheng tsena ka bobeli, ho bile le litlamorao tsa bohlokoa ho subscale ea ARCI MBG (e fokotsehile boiketlo) le sethaleng sa VAS Bad athari tse neng li tsamaellana le litlamorao tse tloaelehileng tsa sethethefatsi sa neuroleptic. Ka kakaretso, sebopeho le boholo ba lintlha le boholo ba liphetho li ne li bapisoa haholo le tse tlalehiloeng lithutong tse fetileng li sebelisa tekanyetso e le 'ngoe ho baithaopi ba phetseng hantle' meleng (Enggasser and de Wit, 2001; Wachtel et al, 2002).
Ha u nahana ka liphetho tsa ba bechang, haloperidol e ntlafalitse litholoana tse monate tsa papali ea slot joalo ka ha e bonts'itsoe ke Monate oa thabo, thabo, le karolo e kenyelletsang.. Moelelo o kopantsoeng oa likamano tse ka tlase ho likalo tse tharo e ne e le r2 = 0.66, bakeng sa ba bechang, e neng e bonts'a hore tšusumetso e tloaelehileng ea papali e bile hoo e ka bang karolo ea mashome a mabeli a metso e meraro ea palo e tlase ea palo, athe karolo e le 'ngoe ho tse tharo ea tsona phapang e ne e ikhethile ho setheoana se seng le se seng.
Haloperidol ka boeona e ne e se na phello e matla ho Takatso ea pele ho papali ho Gamble mathateng a papali ea chelete. Tlas'a placebo, papali ea mochini oa slot e ile ea eketsa Takatso ea Gamble le haloperidol haholo e ntlafalitse ts'ebetso ena ea pele ho ba bechang. Kahoo, haloperidol e bile le litlamorao tse sa fetoheng ho mahlakore a nang le moputso le a susumetsang a papali ea slot mochini, sebopeho se netefatsang mefuta e 'meli ea indices. Haloperidol e boetse e ntlafalitse boteng ba mantsoe a papali ea chelete ho latela mantsoe a Neutral, joalo ka ha ho bonts'oa ke likarabo tsa ho bala tse potlakileng ho Lexical Salience Task. Mabapi le ts'ebetso ea 'mele. mochini oa slot o lebisitse keketseho e kholo ea khatello ea mali tlasa placebo le haloperidol li matlafalitse phello ena. Kahoo, haloperidol e ile ea eketsa melemo e tlatsetsang, e matlafatsang le e matlafatsang ea ho becha ho papali ea papali ea chelete. Liphetho li ne li hlakile ebile li fetoha kamehla ha ho itlaleha, likarabo tsa ho bala ka boiketsetso le li-indices tsa khatello ea mali.
Liphetho tse 'maloa tsa taolo li ne li tsamaisana le tsa ba bechang. Taba ea mantlha, ho li-control, haloperidol ka boeona e ne e se na phello e matla ho Takatso ea pele ho papali ho Gamble. Ntlha ea bobeli, tlasa placebo, papali ea mochini oa slot e hatisitse takatso ea Gamble le ho eketsa khatello ea mali ea systolic maemong a taolo. Ts'ebeliso ena ea morao-rao e lumellana le liphumano tse boletsoeng esale pele tsa likarabo tse phahameng tsa kutloelo-bohloko tsa adrenal bothateng le ho se nang mathata nakong ea papali ea papali ea casino (Meyer et al, 2004). Qetellong, haloperidol e ile ea ntlafatsa litlamorao tsa papali lipapaling le boholo ba phello ea lithethefatsi e batla e tšoana le ea ba bechang.
Ho fapana le papali ea chelete, ho li-control, haloperidol ha e a ka ea natefisa litlamorao tse monate tsa papali, e ile ea tsosa takatso ea ho becha kapa ho kopanya hape mantsoe a papali ea chelete ho Lexical Salience Task. Kahoo, lithutong tse laoloang bao e neng e hlile e se baetsi ba papali ea chelete, ntlafatso ea haloperidol ea ts'ebetso ea 'mele e bonahala e sa arolelanoe le litlamorao tsa karabelo tse matlafatsang tsa ts'ebetso ea papali ea papali ea chelete. Leha ho le joalo, lithuto tsa taolo li ile tsa bonahala li fumana ho bapala mochini oa slot ho tiisa, joalo ka ha ho thathamisitsoe ke litlamorao tse monate tsa papali le papali ea Desire ho Gamble tlasa placebo. Ha ho hlake hore na ke eng e entseng hore ho se kopane ho litlamorao tsa haloperidol lithutong tsa 'mele le ho fumana meputso maemong a laolang ao e seng a papali ea chelete. Sena se hlahisa potso ea hore na haloperidol e ka ama batho ba papali ea papali ea chelete joang papisong ena ea liteko. Ho ka etsahala hore nalane ea papali ea chelete le likarabo tse lumellanang kapa mamello e ka tlatsetsa liphellong tsa haloperidol ho matlafatsong ea papali ea chelete. Ho na le bopaki bo teng lipatlisisong le liphoofolo hore sisteme ea dopamine le D2 receptor ka ho khetheha li bapala karolo e fapaneng ho matlafatsong ea thepa e khothalletsoang lithutong tse lemalloang tse sa amaneng le litaba (cf. Dockstader et al, 2001).
Ho fumana hore karolo e itseng ea D2 blockade e ntlafalitse melemo ea papali ea chelete ea ho becha ho papali ea papali ea chelete, e kanna ea makatsa. Ha ho fanoa ka ho tšoana ho teng ha li-neurochemical lipakeng tsa papali ea chelete ea ho becha le psychostimulant (Zack le Poulos, 2004), lipatlisiso ka litlamorao tsa bahanyetsi ba dopamine ka moputso oa psychostimulant li bohlokoa.
Patlisiso e batsi le liphoofolo e sebelisang mefuta e fapaneng ea lipapatso e fumane hore D2 blockade e sa fetoheng e fokotsa ts'ebetso e matlafatsang ea lithethefatsi tsa psychostimulant (Amit le Smith, 1992; Bari le Pierce, 2005; Britton et al, 1991; Caine et al, 2002; Fletcher, 1998).
Ka lithuto le batho, litlamorao tsa bahanyetsi ba D2 ho moputso oa psychostimulant ha li lumellane. Lithuto tse ling ha li fumane phello (mohlala, Brauer le de Wit, 1997; Wachtel et al, 2002); ba bang ba fumane moputso o fokotsehileng oa psychostimulant (mohlala, Gunne et al, 1972; Jonsson, 1972; Sherer et al, 1989); 'me thuto e le' ngoe e fumane moputso o eketsehileng oa psychostimulant (Brauer and de Wit, 1996). Thutong ea bona ea lingoliloeng tsa psychostimulant, Brauer et al (1997) ba bua ka ho haella ha mangolo pakeng tsa phoofolo le lipatlisiso tsa batho mabapi le dosing e sebetsang le phapang e fapaneng ea mokhoa. Ka lebaka la sena, tlhahlobo ea karabelo ea tekanyetso ea litlamorao tsa haloperidol mabapi le ts'ebeliso ea papali ea chelete e ka ba tlatsetso ea bohlokoa potsong ea joale.
Bopaki ba lithuto tse natefisang, leha ho le joalo, bo bonahala bo lumellana le se fumanoeng hona joale bakeng sa ba bechang. Boithuto bo bongata, Volkow et al (1999, 2000) e fumane hore ho fumaneha ha li-receptor tsa D2 tse tlase ho ne ho hokahane ka nepo ho bile le melemo e meholo ea moputso oa psychostimulant, methylphenidate ho baithaopi ba phetseng hantle. Ka mantsoe a mang, ha ho fumaneha ha li-receptor tsa D2 ho le tlase, ho ne ho khahlisa lithethefatsi. Hape, joalo ka ha ho boletsoe pejana, liphetho tsa hajoale li tšoana le 'ho makatsang' pejana ho fumana hore kalafo ea pele ho moo ka 1- kapa 2-mg ea mohanyetsi oa D2, pimozide e ekelitse khethollo le ho 'rata' tekanyetso ea 20-mg ea d- amphetamine ho baithaopi (Brauer le de Wit, 1996).
Ho khahlisang ke hore thutong e arohaneng, Volkow et al (2003) o fumane hore keketseho e bakoang ke methylphenidate ea khatello ea mali e ne e amana haholo le plasma epinephrine le keketseho ea striatal dopamine. Ba khothalelitse hore litlamorao tsa khatello ea methylphenidate li ne li le lipakeng tsa keketseho e bakoang ke DA ho epinephrine ea pheriferale. Tlaleho ena e hlahisa monyetla oa hore ho phahama ha khatello ea mali e bakoang ke papali ea chelete tlasa haloperidol thutong ea hajoale ho kanna ha bonts'a bophahamo ba striatal dopamine le litlamorao tse tšoanang ho epinephrine.
Joalokaha ho boletsoe ho Selelekela, lithuto tsa lefutso li fane ka bopaki bo amanang le hore mosebetsi o tlase oa D2 receptor ke sesosa sa kotsi sa nts'etsopele ea ho betla ha pathological (Comings et al, 1996). Patlisiso e ileng ea latela ea FMRI le baithaopi ba phetseng hantle ba fumane hore ba nang le liphatsa tsa lefutso (A1 allele) e amanang le ts'ebetso e nyane ea D2 receptor e bonts'itse ts'ebetso e eketsehileng ho meputso e lebelletsoeng libakeng tse amanang le moputso nakong ea papali ea papali ea chelete. (Cohen et al, 2005).
Liphumano tse teng hona joale li atolosa moeli oa lipatlisiso o sebelisang mokhoa oa bongaka ho bonts'a hore phallo ea D2 e fumanehang ka tlase ke sethethefatsi e ntlafatsa litlamorao tsa mochini oa slot ho tsa papali ea papali ea chelete. Liphetho tsena li lumellana le se fumanoeng ka neuroimaging se boletsoeng ka holimo, 'me se fana ka bopaki ba liteko ba kamano ea methapo-kutlo e ka fokotsang kamano pakeng tsa ba sa tsotelleng mefuteng ea D2 ea li-receptor le ho ba kotsing ea ho becha.
Ha ho fanoa ka ho tšoana ho teng pakeng tsa neurochemical lipakeng tsa papali ea chelete ea ho becha le psychostimulant (Zack le Poulos, 2004), liphetho tse teng li fana ka maikutlo a hore likarolo tse ling tsa dopamine tse fetotsoeng ke D2 le ho susumetsa ts'ebetso ea psychostimulant, mohlala, D1 le D3 receptors (Xu, 1998) hantle ba bohlokoa molemong oa ho tiisa papali ea chelete. Qetellong, liphetho tsa hona joale li fana ka maikutlo a hore lithethefatsi tse ntlafatsang phetisetso ea dopamine setsing sa katlase sa D2 li kanna tsa tšepisa bakuli bakeng sa ho etsa lipatlisiso tsa meriana bakeng sa papali ea papali ea methapo ea methapo.
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