Neuropsychopharmacology (2007) 32, 1678-1686; doi: 10.1038 / sj.npp.1301295; waxaa la daabacay 3 January 2007, Martin Zack1,2,3 iyo Constantine X Poulos4, Waraaqaha: Dr M Zack, Qaybta Nuujiyaanka Qaybta, Xarunta Ku-Xeelaysiga iyo Caafimaadka Maskaxda, 33 Russell Street, Toronto, ON, Canada M5S 2S1.
aan la taaban karin
Cilmi-baaristii hore waxay muujisay dusha sare ee la wadaago ee qamaarka iyo abaalmarinta nafsaaniga ah. Tani waxay soo jeedinaysaa in substrates dopamine ay si toos ah u xakameyn karaan geeddi-socodka xoojinta ee khamaarka noolaha.
Si loo baaro arinkan, daraasadani waxay qiimeysay saameynta dopamine DXXUMX antagonist, haloperidol (2 mg, afka) ka jawaab celinta khamaarka dhabta ah (3 min mashiinka xargaha) ee 15 khamaarayaasha nafsaaniga ah ee non-comorbid and 20 non- qamaarayaasha xakamaynta xuduudaha la xakameynayo, indhoole indhoole ah, naqshadayn leh.
Khamaarayaasha, haloperidol waxay si weyn u kordhinayaan saameynta abaalmarinta ee khamaarka, khadadka ka dambeeya rabitaanka khamaarka, fududeynta xawaaraha akhrinta erayada khamaarka, iyo khamaarka khalkhalka ku jira ee cadaadiska dhiigga. Xakamaynta, haloperidol qoynta qulqulaya cadaadiska dhiigga, laakiin wax saameyn ah kuma yeelanin indices kale. Natiijooyinka waxay bixiyaan cadeyn toos ah oo tijaabo ah oo ah in D2 substrate ay xakamayso khamaarista cudurada wadnaha.
Keywords:
khamaarka, dopamine, D2, haloperidol, abaal-marin, dallacsi
HORDHAC
Khamaarka nafsaaniga waa cudur maskaxeed oo badiyaa keeni kara cawaaqib xun (Morasco et al, 2006; Scherrer et al, 2005). Caddeynta la xidhiidha dhexdhexaadiyayaasha neerokimiga ee saameynta ama xoojinta saameynta ciyaaraha khamaarka laftiisa ayaa bilaabay inay soo baxaan. Cilmi baaristii ugu dambeysay ee fMRI waxay ogaatay in ciyaar khayaali u eg oo qiyam lacageed ah ay dhaqaajineyso nidaamka abaalmarinta mesolimbic ee khamaarayaasha cudurada iyo kontaroolada (Reu ter et al, 2005). Daraasadani waxay ogaatay in firfircoonida mesolimbic ee ciyaarta sababtay ay ka hooseyso khamaarayaasha marka loo eego kontaroolada, iyo sida ugu daran ee loo yaqaan 'pathology', khafiifinta firfircoonida ciyaarta. Baarayaasha waxay u fasirteen natiijooyinkooda inay la jaan qaadayaan 'cillad yaraanta abaalmarinta' khamaarayaasha cudurada wadnaha.
Shaqooyinka kale waxay ogaadeen inay ku jiraan casino dhab ah khamaarka wuxuu xoojiyaa dhaqdhaqaaqa farsamooyinka hypothalamic-pituitary ee dhibaatada iyo khamaarka aan dhibaatooyinka lahayn, sida ay ka muuqato heerarka plasma ee kordhiya norepinephrine, cortisol, iyo kororka xoojinta garaaca wadnaha (Meyer et al, 2004). Intaa waxaa dheer, khamaarka khamaarka wuxuu u horseeday heerarka sare ee dopamine ee labada kooxood, oo leh heerar sare oo ka soo baxa qamaarayaasha dhibaatada leh.
Qaab kale oo baaritaan ah ayaa loo adeegsaday istaraatiijiyad isdhaafsasho farsamo ah si loo soo koobo dhexdhexaadiyeyaasha guud ee neurochemical ee khibradda khamaarka (Zack iyo Poulos, 2004). Daraasaddan ayaa lagu ogaaday in dopamine dopamine agonist, d-amphetamine, dhiirigelinta doorbidan ee loo adeegsado khamaarista qamaarka cudurada wadnaha. Natiijadani waxay muujinaysaa dusha sare ee jirka ee khamaarka iyo kharashka nafsaaniga ah. Tani waxay soo jeedineysaa in, sida kiiska nafsaaniga ah, firfircoonida waxyaabaha loo yaqaan 'dopamine substrates' ay si toos ah u maamuli karto geedi socodka xoojinta khamaarka noolaha. Caddaynta arrintani waxay muhiim u tahay fahamka khamaarka saamaynta u leh balwadda ee shakhsiyaadka nugul.
Daraasad weyn oo cilmi-baaris ah ayaa waxay soo bandhigtay qiyaasta D2 sida abaal-marin qallafsan oo maskaxeed (Nader iyo Czoty, 2005; Self and Stein, 1992; Volkow et al, 1999, 2002). Intaa waxaa dheer, baaritaanka ku saabsan bini-aadamka u nugul qanjirka ayaa xoojiyay muhiimada ay leedahay D2 in uu qaato halista hidde-qabta (Comings et al, 1996). Tani waxay la socotaa cilmi-baaris kale oo muujinaysa xiriir adag oo udhaxeeya astaamaha lagu garto unugyada D2 iyo halista ah noocyo kala duwan oo isku-dhafan oo khasab ah (Blum et al, 1995, 1996).
Daraasadaha neuroimaging waxay si joogta ah u heleen maqnaashaha D2-ga oo ku xiran (sida helitaankoodu yar yahay) shakhsiyaadka muujiya cudurrada addictive-compulsive, oo ay ka mid yihiin daroogada kookeynta iyo methamphetamine (Volkow et al, 1990, 2001), heroin-tako (Wang et al, 1997) (Volkow et al, 1996), iyo buurnaanta (Wang et al, 2001).
Natiijadan qaab-dhismeedkan ayaa kor u qaaday falsafada muujinaysa in ay adag tahay in la raadiyo xoojiyeyaasha dhiirrigeliyeyaasha ah inay metelaan jawaab celin buuxda oo ku saabsan foosha loo yaqaan 'genetically mediated' ama daroogada sababtoo ah daroogada 'D2' (sida Grace, 2000; Noble, 2000; Volkow et al, 2004).
Iyada oo tan la mid ah, khamriga oo leh heerarka hoose ee Digniinayaasha D2 ayaa muujinaya xiisa badan oo muujinaya firfircoonida koontooyinka hore ee saxda ah iyo xuduudaha kore ee maskaxda ah ee ku lug leh dhiirigelinta iyo feejignaanta (Heinz et al, 2004). Cilmi-baareyaasha PET, cilmi baarista PET waxay muujinaysaa in soo-gaadhista cocaine-ka ay kordhinayaan dhaqdhaqaaqa dopamin-ta ah ee D2 oo ku yaala qanjirada dulinka ah iyo baaxadda saameyntani waxay saadaalisay inay rabto (Volkow et al, 2006). Natiijooyinkaasi waxay soo jeedinayaan in shakhsiyaadka leh heerarka hooseeya ee DPP-yada D2 ay aad ugu nugul yihiin dhiirrigelinta dhiirigelinta iyo in heerarka sare ee dopamine ee kuwa soo-dhoweeyayaashu ay si toos ah u dhexdhexaadin karaan geeddi-socodkan.
Marka la eego caddaynta ku saabsan muhiimada D2 looyaqaan ee khamaarka dhibaatada leh iyo dhibaatooyinka kale ee addoon-darrada ah, daraasaddan hadda waxay baaris ku samaysay saameynta dufanka D2 ee xaglaha ah, haloperidol oo ku saabsan jawaabaha gaaban gaaban ee mashiinka gawaarida ee khamaarka noolaha iyo kantaroolka caafimaadka leh .
MATERIALS AND METHODS
Astaamaha Mawduuca
Labaatan (seddex dumar ah) oo aan daaweyn raadineynin khamaarayaasha cudurada wadnaha, oo aan lahayn wax dhib ah oo ku saabsan baaritaanka baaritaanka, iyo 18 (afar haween ah) kontaroolo caafimaad leh, ayaa lagu qorey xayaysiisyada wargeysyada waxaana lagu siiyay kaqeybgalka. Khamaarayaasha waxaa si cad loogula taliyay in daraasadda aan loogu talagalin in lagu daaweeyo dhibaatooyinkooda khamaarka. Dhammaan maadooyinka waxay soo mareen baaritaan dhakhtar kahor baaritaanka. Da'da muunada waxay ahayd 21-64 (M = 38.9, SD = 11.7) sano. Ma jirin kala duwanaansho kooxeed oo ku saabsan doorsoomayaasha tirakoobka dadka. Labada koox midkoodna muu muujin heerarka caafimaad ee ku habboon ee walwalka, niyadjabka; isticmaalka khamriga ama daroogada. Cabitaannada celceliska (SD) / usbuuc waxay ahaayeen 2.8 (2.4) khamaarayaasha iyo 1.6 (1.9) xakameynta. Dhibcaha celceliska (SD) ee qaabka Beck Depression Inventory-short (Beck and Beck, 1972) waxay ahaayeen 3.6 (3.1) khamaarayaasha, iyo 1.1 (1.9) ee kontaroolada.
Dhamaan khamaarayaasha waxay ku dhufteen 5 (M = 11.0, SD = 4.4) ee loogu talagalay khamaarka loo yaqaan Pathm-IV Pathological Feel (Beaudoin iyo Cox, 1999). Qiimaha khamaarka khamaarkooda waxay ahaayeen kuwo la taaban karo. Kharashka toddobaadlaha ah ee kharashka khamaarka wuxuu ahaa $ 279 (266), oo u dhiganta 20.3% (12.4) ee dakhligooda, iyadoo celcelis ahaan lumay dhibtii ugu badnayd munaasabadda $ 7563 (22 179). Xakamaynta dhammaan 0 ayaa ku dhacday DSM-IV, oo ku qaatay $ 1.0 (1.3) toddobaadkii khamaarka, waxaana lagu soo warramay celcelis ahaan khasaaraha ugu badnaan ee munaasabadda $ 7.1 (8.4). Sidaa darteed, koontaroolayaashu waxay ahaayeen kuwo aan qamaar lahayn. Ciyaartoyda khamaarka ah, waxqabadyo khamaaris oo joogto ah waxay ahaayeen: ciyaaraha casino (15 / 20), xargo (12 / 20), isboorti (8 / 20), farasaarayn (6 / 20), bakhtiyaanasiib (4 / 20), iyo bingo (1 / 20 ).
Miisaanka iyo Qalabka
Miisaanka analogga ah (VAS; 0-10; Aan ahayn Dhamaan Dhibaatada) lagu qiyaaso Saameynta Fiican iyo Saameyn xun ee Kaabsaydhka. Xarunta Cilmi-baarista Isticmaalka Addiction (ARCI; Haertzen, 1965) waxay bixisay tallaabooyin la isku daro oo saameyn ku leh daroogada, iyo qaabka gaaban ee Profile of Mood States (POMS, Shacham, 1983) waxay qiyaaseen gobolo kala duwan.
VAS ayaa sidoo kale qiyaastay saameynta la raaxeysan karo (Raaxo, Farxad, Ka Qayb-galka) ciyaarta mashiinka gawaarida, iyo sidoo kale rabitaanka Faraxiga.
Hawlaha akhrinta degdegsan (Lexical Salience Task) oo lagu qiyaaso waqtiga jawaab celinta akhriska (oo ku jirta ms) si loo yareeyo ereyada khamaarka (tusaale, w * a * g * e * r) ereyo dhexdhexaad ah (eg w * i * n * d * o * w) . Hawsha iyo dareenka waxay la mid yihiin kuwa ku faahfaahsan daraasad hore (Zack iyo Poulos, 2004). Soodejinta waxaa loo qeexay sida farqiga udhaca akhriska ee loo yaqaan "Gambling vs Words".
Mashiinka ganacsiga ee hadda loo adeegsado casinos-ka Ontaariyo ('Cash Crop'; WMS Gaming Inc., Chicago, IL) ayaa u adeegay sidii ra'iisul dhiirrigelin. Mawduucyadu waxay soo jiidan karaan 1 - 45 dhibco / wareejin, waxaana loo sheegay inay heli doonaan gunno lacageed oo u dhiganta xisaabtankoodii ugu dambeeyay ee kulan kasta.
Cadaadiska dhiigga waxaa lagu qiimeeyay naqshad caarad ah (HEM-601 Omron Inc, Vernon Hills, IL).
Xulashada Haloperidol sida Dopamine D2 Probe
Haloperidol (3 mg, afka ah) wuxuu keenaa 60-70% D2 qaataha degenaanshaha wuxuuna gaaraa heerarka dhiigga ugu sareeya 2.75 h ka dib maamulida (Nordstrom et al, 1992). Difaacayaasha 'dopamine antagonists' ee loo heli karo isticmaalka aadanaha ee Kanada, haloperidol (gaar ahaan qiyaasta subclinical ee loo adeegsaday daraasaddan) ayaa ah xulashada ugu badan ee loo yaqaan 'D2 receptor'. Macluumaadka 'vitro data' ee laga helo jiirka iyo unugyada bini'aadamka ee isku xira (Arndt iyo Skarsfeldt, 1998; Schotte et al, 1996) waxay muujinayaan in isku xirnaanta haloperidol ee D2 ay 15 jeer ka weyn tahay D3, daawada loo yaqaan 'dopamine reseptor' oo ay ku leedahay xigtada ugu weyn; 9–13 jeer ka weyn -1 adrenoreceptor; iyo 18-34 jeer ka weyn kan loo yaqaan 'serotonin 2A receptor'; iyada oo aan lahayn xidhiidh la mahadiyo oo loogu talagalay goobaha kale ee ku xidha gudbiyaha. Daraasadaha maskaxda bini'aadamka dhimashada ka dib (Richelson iyo Souder, 2000) waxay muujinayaan isku xirnaan dhexdhexaad ah -1 adrenoreceptor (15% isku xirnaanta D2). Waxyaabaha laga reebi karo ee ku saabsan qaabkan doorbidista mudnaanta leh ayaa ah qaataha sigma, kaas oo haloperidol uu ku xirmo qiyaas ahaan isku mid ahaansho sida soo-dhoweynta D2 (Schotte et al, 1996). Tani waxay gacan ka geysan kartaa awooddeeda ah inay joojiso mala-awaalka (cf. Keats iyo Telford, 1964).
Nidaamka
Daraasadan waxaa lagu fuliyay heerarka anshaxa ee Bayaanka Helsinki (1975). Ka dib markii ay bixiso ogolaansho wargalin, mawduuc ayaa ka qeybgalay laba kalfadhi imtixaan, 1 isbuucii (si loo hubiyo dhar dhaqidda), halkaasoo ay ku heleen 3 mg haloperidol ama placebo oo ah naqshad labanlaab ah, oo qaabaysan.
Xilliga imtixaanka oo dhan, 2.75 h ka dib markii la qadimay, maadooyinka ayaa mashiinka xargaha oo leh $ 200 ee dhibcaha ee shaybaar-bar-baaris. Waxay khamaaraan 15 min ama ilaa deymahooda la dhammeeyey.
ARCI iyo POMS ayaa loo maamulay ka hor, ka dibna mar kale ka hor ciyaarta ciyaarta mashiinka ah ee heerarka daaweynta dhiigga oo sareeya. Desire to Gamble ayaa lagu qiimeeyay labadan jeer iyo sidoo kale midig ka dib ciyaarta ciyaarta mashiinka. Dhibaatooyinka la heli karo ayaa la qiyaasay ka dib markii qalabka casriga ah ee la raacay si dhakhso ah ayadoo loo marayo Hawlaha Sare ee Shaqada. Cadaadiska dhiigga ayaa lagu qiyaasay saacadaha 30-min inta lagu jiro kalfadhiga.
Si loo yareeyo saameynta macquulka ah ee muraayada mishiinka, maadooyinka ayaa ku sugnaa sheybaarka 4 h ka dib markii baaritaanka la dhammeeyey. Waxaa lagu qiimeeyay kalkaalisada diiwaangashan ka hor inta aan shaqada laga eryin waxaana loo diraa guriga iyadoo loo marayo taksi. Marka la joojiyo, maadooyinka waxay heleen qiyaasta 50-mg ee diphenhydramine (Benadryl) si ay u isticmaasho haddii ay dhacdo dareen-celin dystonic ah oo soo daahday.
Nidaamka falanqaynta xogta
Saamaynta celceliska waxaa lagu qiimeeyay 2 (Daaweynta: Daroogada, placebo) 2 (Kooxda: khamaarayaasha, kontaroolada) falanqaynta kala duwanaanta (ANOVA). Meesha ay ku habboon tahay, doorsoomayaasha maaddooyinka dhexdooda ah ayaa lagu soo daray ANOVA (tusaale, xaaladda ereyga ee Hawsha Saalixada Lexical). Loogu talagalay doorsoomayaasha halkaasoo laga heli karo dhibcaha aasaasiga hore ee kaabsalka (VAS ratings of Desire to Gamble), falanqaynta kala duwanaanshaha (ANCOVA) ayaa la sameeyay, iyadoo la adeegsanayo dhibcaha aasaasiga ah ee wada-duwanaanshaha, si loo xakameeyo kala duwanaanta tijaabada ah ee dheeraadka ah iyo in la go'doomiyo saameynta daaweynta (Wainer , 1991).
Natiijooyinka
Saameynta Kaadida
Si loo qiimeeyo wax ku oolnimada indhoolayaasha, dhamaadka maadooyinka daraasadda ayaa la weydiiyay inay soo sheegaan maalinta ay rumeysan yihiin inay heleen daroogada. A 2 (Isku xigxiga Daaweynta: Daroogada Fadhiga 1, Daroogada Kulanka 2) 3 (Xulashada Jawaabta: Rumayso Maalinta 1, Rumayso Maalinta 2, Ma Ogi) 2 jawaabaha muunada oo dhami ma ahayn wax muhiim ah, 2 (df = 2, N = 20) = 2.61, p> 0.27. Guud ahaan, maaddooyinka 33/38 ayaa ku jawaabay 'Ma Ogi;' labo si sax ah iyo mid si qaldan loo soo sheegay Kalfadhiga 1; iyo laba Kalfadhi oo si qaldan loo soo sheegay 2. Qaabka kuma kala duwana khamaarayaasha iyo kontaroolada, 2 <2.3, p's> 0.32, oo leh hal warbixin oo sax ah oo ku saabsan khamaarayaasha, iyo mid ku jirta kantaroolka. Marka, maadooyinka kama takoori karaan daroogada placebo, sidaa darteed wixii khilaafaad ah ee ka jawaab celinta mashiinka qaawan kuma xirna saameynta loo maleynayo ee ah inuu ku hoosjiro saameynta daroogada xoojinta khamaarka.
Shaxda 1 waxay muujineysaa saameynta nafsiga ah ee kaararka ku salaysan ARCI, POMS, iyo VAS ee 2.75 h ka dib markii la qiyaasayo (heerarka daroogada ee haloperidol) oo ay weheliso dhibcaha horay u-soo-kabashada ee daaweyn kasta ee khamaarayaasha iyo kontoroolayaasha.
Jadwalka 1 - Micnaha (SD) Saamaynta Mawduuca ee Kaabsulka (3 mg Haloperidol; placebo) Heerarka Dhiigga ugu Sarreeya (2.75 h Maamulka-dambeeya) ee miisaanka-hoose ee ARCI, POMS (qaab-gaaban), iyo Miisaanka Muuqaalka Analogga (Wanaagsan) / Saamaynta Xun; 0-10) Mawduucyada Xakamaynta Caafimaadka (n = 18) iyo Khamaarayaasha Cudurka Jirka (n = 20).
ARCI
A 2 (Kooxda) 2 (Daaweynta) 2 (Waqtiga) 7 (Tirada hoose) ANOVA ee qiimeynta ARCI waxay keeneen saameynaha soosocda ee laxiriira daaweynta: Isdhexgal Waqti Daaweyn oo muhiim ah, F (1, 216) = 5.50, p = 0.025, iyo a isdhexgal hoose oo muhiim ah Waqtiga Daaweynta, F (6, 216) = 2.06, p = 0.060, oo aan laheyn saameyn kale oo muhiim ah oo ku lug leh Daaweynta, p's> 0.50. Isdhexgalka Waqtiga Daaweynta wuxuu muujiyey hoos udhac guud ee dhibcaha pre-kaabsol ilaa kaabsal-ka hooseeya haloperidol iyadoo ka soo horjeedda kororka guud ee dhibcaha laga soo bilaabo ka-hor-kaabsalka hoosta placebo. Sida ku cad Jadwalka 1, isdhexgalka saddexda geesood ee muhiimka u ah ayaa ka tarjumaya dib-u-habeyn xulasho ah oo ku saabsan qaabka dhibcaha miisaanka hoose ee MBG, kaas oo u muuqday inuu ka sii kordhayo ka-hor-kaabsalka ka-hooseeya placebo ee khamaarayaasha oo keliya, laakiin hoos ayuu uga dhacay labadaba kooxaha ka-soo-hor-kaabsalka ka hooseeya haloperidol. Jihada saamaynta iyo cabirka saamaynta buuxda ee isuduwaha kaladuwan ayaa si aad ah ula jaan qaadaya cilmi-baaris hore oo tijaabisay qiyaasta 3-mg ee haloperidol ee mutadawiciinta caafimaadka qaba (Enggasser iyo de Wit, 2001; Wachtel et al, 2002). Saameyn weyn oo muhiim ah oo ku saabsan Kooxda, F (1, 36) = 5.46, p = 0.025, ayaa muujisay xoogaa sare celcelis ahaan celcelis ahaan (SD), iskudarka guud ee Xeerarka iyo Daaweynta, khamaarayaasha, 3.8 (0.8), marka loo eego kontaroolada, 3.2 (0.8) ).
POMS
A 2 (Kooxda) 2 (Daaweynta) 2 (Waqtiga) 6 (Tirada hoose) ANOVA ee qiimeynta POMS wax saameyn ah oo weyn kuma lahan daaweynta, p's> 0.10.
VAS
A 2 (Kooxda) 2 (Daaweynta) 2 (Subscale) ANOVA ee dhibcaha VAS waxay dhalisay isdhexgal hoose oo muhiim ah oo ku saabsan Iskuduwaha Iskuduwaha, F (1, 36) = 3.44, p = 0.072, oo aan laheyn saameyn kale oo laxiriira Daaweynta, p's> 0.56 . Jadwalka 1 wuxuu muujinayaa in natiijadani ay ka tarjumeyso koror dhexdhexaad ah oo isdaba-joog ah oo laga soo sheegayo Saamaynta Xun ee koox kasta oo ka hooseysa haloperidol vs placebo, halka dhibcaha Saameynta Wanaagsan aysan beddelin si qadarin leh daaweynta daroogada.
Saameynta ciyaaraha kubbadda qalabka
Dhibaatooyinka la isku soo bandhigay ee ciyaarta
Jaantuska 1 wuxuu muujinayaa qiimeynta celceliska (SEM) ee khamaarka ku-raaxeysiga, Farxadda, iyo Ka-qaybgalka waxayna muujineysaa in haloperidol ay kordhisay dhibcaha miisaanka kasta ee qamaarayaasha, laakiin uma muuqan inuu wax ka beddelayo dhibcaha si mahadcelin leh ee kantaroolka ah. Indha-indhayntan waxaa lagu xaqiijiyey falanqaynta. A 2 (Kooxda) 2 (Daaweynta) 3 (Subscale) ANOVA waxay soo saartay saameyn weyn oo muhiim ah oo ah Kooxda, F (1, 36) = 6.36, p = 0.016, Isdhexgalka Kooxda Daaweynta, F (1, 36) = 4.17, p = 0.048, oo aan lahayn saameyn sare oo sare, p's> 0.50. Saamaynta kooxdu waxay ka tarjumaysaa dhibcaha ka sarreeya khamaarayaasha marka loo eego kontaroolada guud ee Xeerarka iyo Daaweynta. Isdhexgalka ayaa ka tarjumaya kororka weyn ee dhibcaha Subscale ee hoos yimaada haloperidol ee khamaarayaasha laakiin kuma xirna kantaroolka; iyo la'aanta saameyno sare oo amar sare leh waxay muujineysaa in haloperidol ay saameyn joogto ah ku kordhisay dhammaan saddexda hoose. Isku celceliska farqiga wadaag ee saddexda hoose wuxuu ahaa r2 = 0.66, khamaarayaasha, iyo r2 = 0.65, kontaroolada. Sidaa darteed, saameyn guud oo lagu farxo ee ciyaarta ayaa lagu qiyaasey saddex-meelood laba ka mid ah kala duwanaanshaha dhibcaha miisaanka hoose, halka qiyaastii seddex meelood meel ka mid ah kala duwanaanshaha uu ahaa mid u gaar ah miisaan kasta.
Jaantus 1.
Micnaha (SEM) iskeed loo soo sheegay ee raaxada leh ee ciyaarta mashiinka mishiinka 15-min ee maadooyinka xakamaynta caafimaadka leh (n = 18) iyo khamaarayaasha cudurada wadnaha (n = 20) ee ku hoos jira haloperidol (3 mg, afka) iyo placebo. * Saamaynta daaweynta daroogada, p <0.001.
Ujeedada is-sheegashada ee khamaarka
Jaantus 2 wuxuu muujinayaa celcelis ahaan (SEM) Rabitaan ku saabsan Qiimeynta Gamble kahor iyo kadib ciyaarta mashiinka ciyaarta. Jaantusku wuxuu muujinayaa in haloperidol kaligeed aysan wax saameyn ah ku laheyn damacii hore ee ciyaar kooxeedkii. Dhibcaha rabitaanku waxay ka soo bilaabeen ciyaarta ka hor ciyaarta ka dambeysa ciyaarta ka dambeysa boos-kooxeed kasta; iyo heerka kor u qaadida ciyaartani waxay u muuqatay inay si weyn uga hooseyso haloperidol khamaarlayaasha laakiin maahan kantarool. Falanqaynta ayaa xaqiijisay aragtidan.
Jaantus 2.
Micnaha (SEM) rabitaanka iskiis loo soo sheegay ee khamaarka kahor iyo kadib ciyaarta mashiinka mishiinka 15-min ee maadooyinka xakamaynta caafimaadka leh (n = 18) iyo khamaarayaasha cudurada wadnaha (n = 20) ee hoos yimaada haloperidol (3 mg, afka) iyo placebo. * Saamaynta daaweynta daroogada, p <0.001.
Hordhac 2 (Kooxda) 2 (Daaweynta) ANOVA ee qiimeynta rabitaanka hore ee kaabsalka (aan la muujin) waxay keentay saameyn weyn oo muhiim ah kooxda, F (1, 36) = 38.39, p <0.001, iyo saameyn kale oo muhiim ah, p's> 0.26, oo ka tarjumeysa udub dhexaad u ah heerka udub dhexaadka (SD) ee aasaasiga ah Rabitaanka Gamble ee khamaarayaasha, 3.6 (1.8) marka loo eego kontaroolada, 0.4 (1.8) kulan kasta oo tijaabo ah. Si loo go'doomiyo saameynta daaweynta (Wainer, 1991), 2 (Kooxda) 2 (Daaweynta) 2 (Ciyaarta Kahor-Post) ANCOVA ee Rabitaanka dhibcaha Gamble waxaa lagu qabtay iyadoo la adeegsanayo buundooyinka 'Desire pre-capsule' oo ah wada-duwanaansho. ANCOVA waxay dhalisay isdhexgal seddex geesood ah oo muhiim ah, F (1, 35) = 4.21, p = 0.048, iyo saameynta ugu yar ee kooxda, p = 0.056, taasoo ka tarjumeysa dhibcaha guud ee ka sarreeya khamaarayaasha marka loo eego kontaroolada.
Falanqaynta saameynta fudud ayaa lagu ogaaday in aysan jirin saameyn weyn oo daaweyn ah oo ku saabsan Rabitaanka ciyaarta kahor ee khamaarayaasha ama xakameynta, p's> 0.50. Placebo hoosteeda, ciyaartu waxay kordhisay dhibcaha Rabitaanka khamaarayaasha, t (35) = 6.31, p <0.001, iyo kontaroolada, t (35) = 3.90, p <0.001. Marka loo eego haloperidol, kororka hore ee boostada ee Desire waxaa si weyn loogu kordhiyay khamaarayaasha, t (35) = 4.13, p <0.001, laakiin kuma xirna kantaroolka, p> 0.50. Sidaa darteed, haloperidol waxay si xushmad leh u xoojisay saameynta horudhaca ah ee ciyaarta mashiinka booska ee khamaarayaasha cudurada wadnaha.
Furitaanka shabakadaha macnaha leh: shaqada salience ee ereyga
Shaxda 2 waxay soo saartaa waqtiga jawaab celinta akhriska (SD) waqtiga jawaab celinta (RT), dhibcaha loogu talagalay ereyada xakameynta khamaarka iyo kuwa dhexdhexaadka ah iyo xaaladaha xannaanaynta ee ku aaddan Xeeldheerta Sare ee Xakamaynta iyo Khamaarayaasha ee Daaweyn kasta. Jadwalku wuxuu muujinayaa in koox kasta oo ka mid ah, RT ay si aad ah ugu yareesay ereyada aan caadiga aheyn marka loo eego dhammaan noocyada kale ee kalmadaha kale ee lagu soo bandhigo placebo iyo haloperidol. Sida hore loo xusay, farqiga udhaxeeya RT ilaa fasalka erayada bartilmaameedka ee ku xiran erayada aan ku habboonayn Ereyada dhexdhexaadka ah ayaa lagu cabbiray salience; farqiga weyn ee (Target Nominal Target), waa kan ugu weyn ee salience.
Jadwalka 2 - Micnaha (SD) Waqtiga Jawaabta Akhrinta (ms) ee loogu talagalay ereyga 'Stimuli' ee khuseeya salience Task Task ee hoostagta placebo iyo Haloperidol (3 mg) maadooyinka laxiriira caafimaadka (n = 18) iyo khamaarayaasha cudurada wadnaha (n = 20).
Miiska buuxa
A 2 (Kooxda) 2 (Daaweynta) 5 (Xaaladda Ereyga) ANOVA waxay soo saartay is-dhexgal saddex geesood ah oo muhiim ah, F (4, 144) = 3.00, p = 0.021. Falanqaynta saameynta fudud ee xakamaynta ayaa lagu ogaaday in farqiga RT ee Neutral ee daroogada iyo placebo uusan si weyn ugu beddelin ereyada Khamaarka, p> 0.06; ku kordhay ereyada khamriga, t (144) = 7.50, p <0.001; oo hoos udhacay labadaba Positive, t (144) = 7.91, p <0.001, iyo erayada Saamaynta xun, t (144) = 11.08, p <0.001. Sidaa darteed, xakamaynta, ereyada khamaarka ma aysan ka muuqan daroogada marka loo eego placebo; Erayada aalkoladu waxay ahaayeen kuwo aad ufiican daroogada, iyo ereyada waxtarka leh, iyadoon loo eegin macnaha, waxay ahaayeen kuwo aan yareyn xagga daroogada. Baadhitaanka dhibcaha xakamaynta Shaxda 2 waxay muujineysaa, placebo, RT ilaa Alkohol ereyada inay si aan caadi aheyn u gaabiyaan marka loo eego ereyada kale ee dhiirrigelinta leh. Marka, farqiga weyn ee u dhexeeya RT ee Khamriga iyo ereyada dhexdhexaadka ah ee haloperidol ee maadooyinkan ayaa si fiican uga tarjumi karay celceliska.
Baadhitaanka dhibcaha RT ee khamaarayaasha xaaladaha kala duwan ee ereyada aan dhexdhexaad ahayn ee hoos imanaya placebo ayaa muujinaya inay guud ahaan aad isugu egyihiin. Falanqaynta saameynta fudud ee khamaarayaasha ayaa lagu ogaaday in haloperidol ay si weyn u kordhisay farqiga RT ee Neutral for Khamaarka ereyada, t (108) = 2.91, p <0.01; iyo ereyada Saamaynta Wanaagsan, t (108) = 5.26, p <0.001; laakiin ma badalin qaraabada RT noocyada kale ee ereyada, p's> 0.50. Sidaa darteed, natiijooyinka khamaarayaasha waxay muujinayaan in ereyada khamaarka iyo ereyada wax ku oolka ah ee wax ku oolka ahi ay aad uga firfircoonaayeen haloperidol marka loo eego placebo
Saameynaha nafsaaniga: cadaadiska dhiigga ee wadnaha
Jaantuska 3 wuxuu muujinayaa saameynta mashiinka mashiinka mashiinka cabbirka cadaadiska dhiigga (mmHg) ee haloperidol iyo placebo ee kontaroolada. Jaantuska 4 wuxuu muujinayaa dhibcooyinka ku habboon khamaarka. Tirooyinkani waxay muujinayaan, in sanduuqa tuubada, cadaadiska dhiigga uu ka kordhay ciyaar ka hor ciyaarta ilaa ciyaarta ka dib labada kooxood. Intaa waxaa dheer, labada kooxba, kororka ciyaarta ee korodhka cadaadiska dhiigga wuxuu ka weynaa haloperidol. Baadhitaanyadani waxaa lagu caddeeyey falanqayn.
Jaantus 3.
Cadaadiska dhiigga (SEM) ee cadaadiska dhiigga (mm Hg) ee xuddunta ka hor iyo koontada 30 inta u dhexeysa kahor iyo ka dib ciyaarta mashiinka 15-min ee mawduucyada ilaalinta caafimaadka (n = 18) ee haloperidol (3 mg, afka) iyo placebo .
Tirada buuxda iyo halyeeyga (15K)
Jaantus 4.
Cadaadiska dhiigga (SEM) cadaadiska cadaadiska dhiigga (mm Hg) ee xariiqa hore ee kiniiniga iyo saacadaha 30 inta ka horreysa iyo ka dib marka la sameeyo mashiinka 15-min ee qalabka casriga (n = 20) ee haloperidol (3 mg, afka) iyo placebo.
A 2 (Kooxda) 2 (Daaweynta) 8 (Waqtiga Imtixaanka) ANOVA ee dhibcaha cadaadiska dhiigga ee dhiig baxa waxay keeneen isdhexgal Waqti Daaweyn oo muhiim ah, F (7, 252) = 2.64, p = 0.012, iyo isdhexgal seddex geesood ah oo muhiim ah, F (7, 252) = 2.89, p = 0.006. Isdhexgalka labada dhinac wuxuu ka tarjumayay koror joogto ah oo ku saabsan saameynta Waqtiga (ciyaarta ka dib laga jaray ciyaarta ugu yar) hoosta haloperidol vs placebo ee kontaroolada, t (252) = 6.15, p <0.001, iyo khamaarayaasha, t (252) = 5.16, p <0.001. Isdhexgalka seddex-geesoodka ah ayaa ka tarjumayay kala duwanaansho kooxeed waqtiga ugu yar ee ciyaarta kahor ay ka dhacday daaweyn kasta. Xakamaynta, cadaadiska dhiigga ee ugu yar wuxuu dhacay 30 daqiiqo kahor bilawga mashiinka booska hoostiisa iyo isla markiiba ciyaarta kahor haloperidol; khamaarayaasha qaabkani waa la rogay, iyada oo ciyaarta ugu horeysa ay dhacdo wax yar uun ka hor bilaabashada ciyaarta hoosta placebo, laakiin 30 daqiiqo kahor ciyaarta bilawga haloperidol. Xusid ahaan, haloperidol waxay ku kordhisay kororka ciyaarta ee sababa cadaadiska dhiigga illaa heer la barbardhigi karo labada koox. Dabeecadda sharadka ee ciyaarta mashiinka mishiinka taxane ah 2 2 ANOVA ee dabeecadda sharadka ee ciyaarta mashiinka mishiinka (macnaheedu waa dhibcaha dhibcaha ee wareegga, ugu badnaan dhibcaha sharad kasta, dhibcaha ugu dambeeya ee la kasbaday) ma aysan keenin saameyn weyn oo ku lug leh Daaweynta, p's> 0.25. Natiijada kaliya ee muhiimka ah waxay saameyn weyn ku yeelatay Kooxda micnaheedu (SD) wadarta wareega / ciyaarta, kuwaasoo aad ugu badnaa khamaarayaasha, 89.4 (39.4) marka loo eego kontaroolada, 60.6 (41.6), F (1, 36) = 9.57, p = 0.004.
DHIBAATOOYINKA
Haloperidol, oo aaney lahayn, wax saameyn ah kuma yeesho qamaarka cudurada wadnaha iyo koontaroolka caafimaadka ee daawada dabiiciga ah ama saameynta niyadda ee sida lagu qiimeeyo saameynta daawada ARCI, POMS, iyo VAS. Labada kooxoodba, waxa jiray waxyaabo aad u muhiim ah oo ku saabsan macaamiisha ARCI MBG (hoos u dhac ku yimid) iyo miisaanka Saamaynta Badbaadinta VAS ee la mid ah saamaynta caadiga ah ee daawada neuroleptic. Guud ahaan, qaabka iyo baaxadda dhibcaha iyo saamiga waxtarka ayaa si aad ah loogu barbardhigay kuwa lagu soo sheegay cilmi-baaristii hore iyagoo isticmaalaya qiyaas isku mid ah oo tabarucayaal caafimaadeed jir ahaaneed (Enggaser iyo de Wit, 2001, Wachtel et al, 2002).
Iyadoo la tixgelinayo marka ugu horeysa natiijooyinka khamaarka, haloperidol waxay kordhisay saameynta raaxada leh ee mashiinka mashiinka gawaarida sida ay ka muuqato Raaxada, Farxadda, iyo Qaadashada Iskuduwaha. Dhexdhexaadinta dhexdhexaadka ah ee saddexda heer-hoosaadku wuxuu ahaa r2 = 0.66, oo loogu talagalay khamaarayaasha, taas oo muujineysa in saameynta guud ee raaxada ah ee ciyaarta ay ka dhigan tahay qiyaas ahaan saddex-meelood laba oo kala duwanaanshaha dhibcaha hoose, halkii saddex meelood meel kala duwanaanshuhu wuxuu ahaa mid u gaar ah heer kasta.
Haloperidol ayaa iska leh saameyn muhiim ah oo ku aadan horay-u-qabashada Khamaarista Khamaarka Qamaarka. Under placebo, ciyaarta mashiinka slot kordhiyey Desire to Gamble iyo haloperidol si weyn u kordhiyay saameynta this saameynta saameynta ee khamaarayaasha. Sidaa daraadeed, haloperidol waxay saameyn joogto ah ku yeesheen qaybaha abaal-marinta iyo dhiirigelinta cayaarta mashiinka mashiinka ah, qaab ah iskudubarid labada nooc ee indices. Haloperidol waxay sidoo kale xoojisay kalsoonida ereyada khamaarka ee la xidhiidha ereyo dhexdhexaad ah, sida caddaynta si dhakhso ah loo fuliyey jawaabaha akhrinta ee ku saabsan Sookeeye Tababarka. Marka la eego dhaqdhaqaaqa jirka, mishiinka dabaysha ayaa horseeday korodh weyn oo ku yimaada cadaadiska dhiigga ee ka yimaada xuddunta iyo haloperidol si weyn u kordhisay saameyntaas. Sidaa darteed, haloperidol waxay kordhisay saameynta, abaal-marinta, iyo saameynta dhaqdhaqaaqa jirka ee khamaarka ku jira khamaarayaasha xannuunka. Saameyntu waxay ahaayeen kuwo cad oo isku dhafan iskood isu sheegid, jawaab celin toos ah, iyo cadaadiska dhiigga.
Natiijooyin dhowr ah oo kantaroolka ah ayaa waxay la jaanqaadaan kuwa kuwa khamaara. Ugu horreyn, kantaroolka, haloperidol ee naftiisa ayaa wax saameyn ah u leh ciyaaraha kahor ciyaarta Desire to Gamble. Marka labaad, kaarka calaamadeynta, ciyaarta mashiinka gaashaan-qaadashada ayaa ujeedkeedu yahay rabitaan khamaar iyo cadaadiska dhiigga ee dhiigbaxa ee kantaroolka. Natiijadan dambe waxay la socotaa horey loo soo ogaaday oo muujinaysa jawaab-celin cadaadis sarreeya oo ku saabsan dhibaatada iyo khamaarka aan dhibaatada lahayn inta lagu jiro khamaarka casabada (Meyer et al, 2004). Ugu dambeyntii, haloperidol waxay kordhisay saameeynta cadaadiska ee ciyaarta ee kontaroolada iyo baaxadda saameynta daroogada waxay la mid tahay kuwii khamaarayaasha.
Marka loo eego qamaarayaasha, ee kontaroolada, haloperidol ma aysan kordhin saameynta wanaagsan ee abaalmarinta cayaarta, rabitaanka dareenka ah ee khamaarka ama falcelinta ee ereyada khamaarka ee ku wajahan Shaqada Sarreysiinta. Sidaa darteed, maaddooyinka kantaroolka ah ee asal ahaan aan ahayn khamaarlay, haloperidol kordhinta dhaqdhaqaaqa jirka ayaa u muuqda in lagu kala saari doono saamaynta ku yeelanaysa jawaab-celinta dhiirigelinta-dhiirigelinta hawlaha khamaarka. Si kastaba ha noqotee, maareynta kumbuyuutarku waxay u muuqdaan in ay ku ciyaaraan mashiinka xargaha si ay u xoojiyaan, iyada oo ay soo bandhigtay saameyno raaxo leh oo la isku soo bandhigay ciyaarta iyo kubbadda loo yaqaan 'Desire to Gamble under placebo. Ma cadda wixii macquul ah ee ka baxsashada saameynta haloperidol on physiological iyo abaalmarinta indices ee ka mid ah kontoroolayaasha aan ahayn-qamaaraha. Tani waxay kicineysaa su'aasha ah sida haloperidol uu saameyn ugu yeelan karo khamaarayaasha bulshada qaabkan tijaabada ah. Waxaa macquul ah in taariikhda khamaarka iyo jawaabaha shuruudaha leh ama dulqaadku ay gacan ka geysan karaan saameynta haloperidol ee xoojinta khamaarka. Waxaa jira cadaymo muujinaya cilmi baarista xayawaanka in nidaamka dopamine iyo D2 ay si gaar ah u ciyaaraan door ka duwan xagga xoojinta sifooyinka indho-indhayneed ee macaamilka iyo maadooyinka aan la xakamayn (Dockstader et al, 2001).
Raadinta ah in xayiraadda D2 ee qayb ka mid ah ay kor u qaadday saameynta dhiirigelinta ee khamaarka ku jira khamaarayaasha xannibmay waxay u muuqan karaan wax aad u la yaab leh. Iyadoo la eegayo muuqaalada nukroorska ee muuqda ee u dhexeeya khamaarka iyo nafsaaniinka maskaxda (Zack iyo Poulos, 2004), baadhitaan ku saabsan saameynta dopamine antagonists ee abaalmarinta nafsiga ah ayaa ku haboon.
Cilmi-baaris ballaaran oo xayawaan ah oo la adeegsanayo noocyo kala duwan oo isbeddel ah ayaa ogaaday Xayiraadda D2 waxay si joogta ah u yareeysaa waxtarka xoojinta daawooyinka nafsaaniga ah (Amit iyo Smith, 1992; Bari iyo Pierce, 2005; Britton et al, 1991; Caine et al, 2002; Fletcher, 1998).
Daraasada aadanaha, saameynta Donge-Rooters ee ku saabsan abaal-marinta nafsaaniga ah ayaa ah mid aan ku haboonayn. Daraasadaha qaar ayaa laga helay wax saameyn ah (sida Brauer iyo de Wit, 2; Wachtel et al, 1997); Qaar kale waxay heleen abaalmarin nafsi ah oo hoos u dhacday (tusaale ahaan Gunne et al, 2002; Jonsson, 1972; Sherer et al, 1972); iyo hal daraasad ayaa ka heshay abaalmarinta masruufka nafsiga (Brauer iyo de Wit, 1989). Dib-u-eegista suugaanta nafsaaniga ah, Brauer et al (1996) waxay ka wada hadashaa aragti la'aanta u dhaxeysa xayawaanka iyo cilmi-baarista bini'aadamka marka loo eego qiyaasta wax-qabadka iyo habab kala duwan. Marka la eego taa, qiimeynta qaadashada daawada haloperidol ee ku saabsan xoojinta khamaarka waxay noqonaysaa qadar qiimo leh oo ku saabsan baaritaanka xaadirka ah.
Caddeyn ka timid daraasadaha neerfiyatka, si kastaba ha ahaatee, waxay u muuqdaan inay la socdaan natiijooyinka imika ee khamaarayaasha. Daraasad taxane ah, Volkow et al (1999, 2000) ayaa ogaaday in helitaanka hoose ee D2 uu ahaa mid si joogto ah uxusantay iyada oo ay saameyn ku yeeshay saameynta faa'iido u leh nafsaaniga, methylphenidate ee mutadawiciimo caafimaad leh. Si kale haddii loo dhigo, ka hooseeya helitaanka soo-dhoweynta D2, ayaa ka weynaa doorbididda daroogada. Sidoo kale, sidii hore loogu sheegay, natiijooyinka imika la helay waxay barbar socdaan raadis hore oo 'ka hor imaad' ah oo daaweyn hore loogu sii daayay 1- ama 2-mg ee D2 antagonist, pimozide waxay kordhisay takoorid iyo 'jeclaan' qiyaasta 20-mg ee d- amfetamiin tabaruceyaal ah (Brauer iyo Wit, 1996).
Arrin xiiso leh, daraasad gaar ah, Volkow et al (2003) waxay ogaatay in kororka dhiig-karka ee methylphenidate uu si aad ah isugu xiran yahay plasma epinephrine iyo kororka dopamine-ka. Waxay soo jeediyeen in saameynta cadaadiska ee methylphenidate ay qayb ka ahayd dhexdhexaadinta DA oo ay sababtay kororka epinephrine dusha sare. Koontadani waxay kor u qaadeysaa suurtagalnimada in sare u qaadista cadaadiska dhiigga ee khamaarka ee hoos yimaada haloperidol ee daraasaddan la joogo ay ka muuqan karto sare u qaadista 'dopamine striatal dopamine' oo leh saameyn u dhiganta epinephrine.
Sida ku xusan Hordhac, cilmi-baarista hidde-qabadka ayaa bixiyay caddaymo is-qilaafsan oo muujinaya in hawlaha hoose ee D2 uu yahay mid muhiim u ah horumarinta khamaarka cudurada (Comings et al, 1996). Cilmi-baarista FMRI ee ku-meel-gaadhka ah ee tabaruceyaasha caafimaadka leh waxay ogaadeen in kuwa qaba genetic variant (A1 allele) ay ku xiran tahay shaqo-qabashada D2 hooseeya oo muujisay dhaqdhaqaaqa sareeya ee abaalmarinta la filayo ee gobollada maskaxda leh ee abaal-marinta inta lagu gudajirayo shaqada khamaarka siman (Cohen et al, 2005).
Natiijooyinka xaadirkan waxay kordhinayaan khadka baaritaanka iyada oo la adeegsanayo hab daaweyneed oo muujinaysa in helitaanka maqaar la'aanta D2 ay soo jiidatay daroogada waxay kor u qaadeysaa saameynta sii xoojinta mashiinka rikoodhada ee khamaarka noolaha. Natiijooyinkani waxay ku qanacsan yihiin helitaanka natiijada neuroimaging ee kor ku xusan, waxayna bixisaa caddayn tijaabo ah oo ku saabsan xiriirka habdhaqanka neurokimiga ee laga yaabo in uu hoos udhaco xiriirka ka dhexeeya anomaliyooyinka ku jira gen genetic receptor genes iyo khatarta khamaarka noolaha.
Marka la eego muuqaalka neurochemical ee u dhexeeya khamaarka iyo nafsaaniga nafsiyan (Zack iyo Poulos, 2004), natiijooyinka imika waxay soo jeedinayaan in dheecaannada kale ee dopamine ee lagu bedelay D2 iyo saamaynta nafsiga maskaxda, tusaale ahaan, duubayaasha D1 iyo D3 (Xu, 1998) waa muhiim inaad ku xoojiso xoojinta khamaarka. Ugu dambeyntii, natiijooyinka xaadirka ah waxay soo jeedinayaan in daawooyinka kor u qaada faafinta dopamine ee substrate D2 laga yaabo in ay noqdaan kuwo rajo gal ah si ay u baaraan daawooyinka loogu talagalay khamaarka noolaha.
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