Neuropsychopharmacology (2007) 32, 1678-1686; doi: 10.1038 / sj.npp.1301295; lofalitsidwa pa intaneti 3 Januwale 2007, Martin Zack1,2,3 ndi Constantine X Poulos4, Makalata: Dr M Zack, Clinical Neuroscience Gawo, Center for Addiction and Mental Health, 33 Russell Street, Toronto, ON, Canada M5S 2S1.
ZOKHUDZA
Kafukufuku wam'mbuyo adawonetsa magawo a neurochemical magawo a juga ndi psychostimulant mphotho. Izi zikusonyeza kuti magawo a dopamine amatha kutsogolera njira yolimbikitsira njuga zamatenda.
Kuti mufufuze nkhaniyi, kafukufuku wapano adayesa zotsatira za woganiza wosankha dopamine D2, haloperidol (3 mg, pakamwa) pazoyankha pamatcheni enieni (15 min pamakina ogwiritsira ntchito) mu 20 osakhala comorbid pathological genases and 18 non- otchova njuga amawongolera kapangidwe kolamulidwa ndi placebo, akhungu awiri, opikisana nawo.
Mwa otchova njuga, haloperidol inakulitsa kwambiri zotsatira zake zabwino za kutchova juga, kutsitsa masewera pambuyo pamasewera okonda kutchova juga, kuthandizira kuwerengera liwiro la mawu a Kutchova Juga, komanso kutchova njuga-kukwezedwa mu kuthamanga kwa magazi. Mukuwongolera, haloperidol ikukulitsidwa kutchova njuga. kuthamanga kwa magazi, koma sizinakhudze mawonekedwe ena. Zomwe zapezazi zimapereka umboni woyeserera mwachindunji kuti D2 substrate modulates kulimbikitsa kutchova juga kwa otchova njuga.
Keywords:
njuga, dopamine, D2, haloperidol, mphotho, priming
MAU OYAMBA
Kutchova njuga ndi matenda amisala omwe nthawi zambiri amatha kubweretsa zowonongeka (Morasco et al, 2006; Scherrer et al, 2005). Umboni wazolowera mitsempha yopindulitsa kapena yolimbitsa ntchito ya njuga palokha wayamba kutuluka. Kafukufuku waposachedwa wa fMRI adapeza kuti masewera onga otchova juga omwe ali ndi mphotho zandalama amathandizira mphotho ya mesolimbic mu otchova njuga ndikuwongolera (Reu ter et al, 2005). Kafukufukuyu adapeza kuti kuyeserera kwa mesolimbic komwe kumachitika ndi masewerawa kunali kochepera mwa otchova juga kuposa owongolera, ndipo zovuta za njuga, zimachepetsa mphamvu zoyambitsa masewerawa. Ofufuzawo adamasulira zomwe apeza kuti ndizogwirizana ndi 'mphotho yakusowa mphotho' mwa otchova njuga.
Ntchito ina yapeza kuti kuchita kasino weniweni kutchova juga kumakweza zochitika za hypothalamic-pituitary axis pamavuto komanso otchova njuga omwe alibe vuto, monga zikuwonetsedwa ndi kuchuluka kwa plasma ya norepinephrine, cortisol, komanso kuwonjezereka kwamlingo woyenda ndi mtima (Meyer et al, 2004). Kuphatikiza apo, kutchova juga kwa kasitomala kunayambitsa milingo yayikulu ya dopamine m'magulu onse awiri, omwe magulu apamwamba amatuluka m'mavuto otchova njuga.
Mzere wina wofunsira anagwiritsa ntchito njira yowerengera mankhwala kuti achulukitse magulu onse amatsenga omwe amalimbikitsa kutchova njuga (Zack ndi Poulos, 2004). Kafukufukuyu adapeza kuti nonspecific dopamine agonist, d-amphetamine, adasankha zomwe adalimbikitsa kuti azichita kutchova juga kwa otchova njuga. Kupeza uku kukuwonetsa magawo amtundu wa neurochemical a njuga ndi psychostimulant mphotho. Izi zikuwonetsa kuti, monga momwe zimakhalira ndi ma psychostimulants, kuyambitsa magawo ena a dopamine kumatha kuwongolera mwachindunji njira zolimbikitsira kutchova njuga. Umboni wa nkhaniyi ndikofunikira kuti mumvetsetse zomwe zimachitika chifukwa cha kutchova juga kwa anthu omwe ali pachiwopsezo.
Kafukufuku wambiri wachititsa kuti D2 receptor ikhale yofunikira kwambiri ya substrate modulating psychostimulant mphotho (Nader ndi Czoty, 2005; Self and Stein, 1992; Volkow et al, 1999, 2002). Kuphatikiza apo, kafukufuku wokhudzana ndi chiopsezo cha juga ya pathological yatsimikiza kufunika kwa D2 receptor pachiwopsezo cha majini ku vuto ili (Comings et al, 1996). Izi zikugwirizana ndi kafukufuku wina wosonyeza kulumikizana kolimba pakati pa anomalies mumtundu womwe code ya D2 receptor ndikuyika pachiwopsezo cha zovuta zingapo zowonjezera-zoyeserera (Blum et al, 1995, 1996).
Maphunziro a Neuroimaging adapeza zoperewera mu D2 receptor binding (kutanthauza kupezeka kochepa) mwa anthu omwe akuwonetsa zovuta zowonjezera-zokakamiza, kuphatikiza kugwiritsa ntchito mankhwala osokoneza bongo a cocaine ndi methamphetamine (Volkow et al, 1990, 2001), uchidakwa wa heroin (Wang et al, 1997), uchidakwa. (Volkow et al, 1996), ndi kunenepa kwambiri (Wang et al, 2001).
Zotsatira izi zalimbikitsa malingaliro oti kufunafuna mokakamiza kwa omwe akuwonjezera makuponi kungayimire kuyankha kotsutsana ndi kusokonekera kwamtundu kapena zoperewera mu D2 receptor function (mwachitsanzo, Grace, 2000; Noble, 2000; Volkow et al, 2004).
Pogwirizana ndi izi, zidakwa zomwe zimakhala ndi ma striatal D2 receptors zimati zikulakalaka kwambiri ndikuwonetsa kuyambitsa kwakukhudzidwa kwambiri kwa medial prefrontal cortex ndi anterior cingate - zigawo zamaubongo zomwe zimathandizira chidwi ndi chidwi (Heinz et al, 2004). Pazosuta za cocaine, Kafukufuku wa PET akuwonetsa kuti kuwonetsa zochitika za cocaine kumawonjezera zochitika za dopamine zamkati ku D2 receptors mu dorsal striatum ndi kukula kwa izi kumaneneratu kulakalaka (Volkow et al, 2006). Zotsatira izi zikuwonetsa kuti anthu omwe ali ndi ziwonetsero zotsika kwambiri za D2 zolandilira amatha kutengeka mosavuta ndi zomwe zimapangitsa kuti ma dopamine atengeke kuzinthu izi.
Poganizira za kufunikira kwa D2 receptor pamavuto amtundu wa juga komanso zovuta zina zowonjezera, kafukufuku wapano adayang'ana zovuta zomwe zimatsutsana ndi otsutsana a D2, haloperidol pamayankho ake pazanthawi kochepa kagawo kagawo ka makina a slot pamayendedwe otchovera njuga .
ZIDA NDI NJIRA
Makhalidwe Omvera
Otsatsa makumi awiri (atatu) osalandira omwe akufuna kutchova juga, osakhala ndi vuto loyesa mayeso, komanso 18 (anayi achikazi) owongolera athanzi, adalembedwa ntchito zotsatsa nyuzipepala ndikulipidwa kuti atenge nawo mbali. Otchova juga adalangizidwa momveka bwino kuti kafukufukuyu sanapangidwe kuti athane ndi mavuto awo a juga. Ophunzira onse adayesedwa ndi dokotala asanayesedwe. Zitsanzo zazaka anali 21-64 (M = 38.9, SD = 11.7) zaka. Panalibe kusiyana kwamagulu pazosiyanasiyana za kuchuluka kwa anthu. Palibe gulu lomwe lidawonetsa kukhudzidwa kwamankhwala pakakhala nkhawa, kukhumudwa; kumwa mowa kapena kugwiritsa ntchito mankhwala osokoneza bongo. Zakumwa (za SD) / sabata (2.8 (2.4) za otchova juga ndi 1.6 (1.9) zowongolera. Kutanthauza (SD) zambiri pa Beck Depression Inventory-short form (Beck ndi Beck, 1972) anali 3.6 (3.1) a otchova juga, ndi 1.1 (1.9) owongolera.
Onse otchova juga adalemba 5 (M = 11.0, SD = 4.4) ya DSM-IV Pathological Kamari (Beaudoin ndi Cox, 1999). Ndalama zawo zomwe amatchova njuga zinali zambiri. Ndalama (SD) zomwe zimagwiritsidwa ntchito mlungu ndi mlungu pa juga zinali $ 279 (266), zofanana ndi 20.3% (12.4) ya zomwe amapeza, kutayika kwakukulu kwapadera pamwambo umodzi wa $ 7563 (22 179). Olamulira onse adaponya 0 pa DSM-IV, adagwiritsa ntchito $ 1.0 (1.3) pa sabata pa juga, ndipo adatinso kutayika kwakukulu pamwambo umodzi wa $ 7.1 (8.4). Chifukwa chake, olamulira anali osachita juga kwenikweni. Pakati pa otchova juga, machitidwe otchovera njuga nthawi zonse anali: masewera a kasino (15 / 20), mipata (12 / 20), masewera (8 / 20), horseracing (6 / 20), lottery (4 / 20), ndi bingo (1 / 20 ).
Makala ndi Zida
Mamba ojambula a analog (VAS; 0-10; Ayi konse-Kwambiri) anayeza Zotsatira Zabwino ndi Zotsatira Zoipa za kaphatikizidwe. The Addiction Research Center Inventory (ARCI; Haertzen, 1965) idapereka muyeso wokhazikika pazotsatira zamankhwala, komanso mawonekedwe afupiafupi la Profile of Mood States (POMS; Shacham, 1983) anayeza zigawo zingapo za mayiko ena.
VAS inayeza nawonso zokondweretsa (Kusangalala, Kusangalatsidwa, Kuphatikizidwa) pamasewera a makina oyendetsa, komanso Desire to Gamble.
Ntchito yowerenga mwachangu (Lexical Salience Task) inayeza nthawi yowerengera (mu ms) ndi mawu osachedwa Kutchova juga (mwachitsanzo w * a * g * e * r) vs Mawu osaneneka (mwachitsanzo w * i * n * d * o * w) . Ntchitoyi ndi zoyambira ndizofanana ndi zomwe zidafotokozedwa kafukufuku wakale (Zack ndi Poulos, 2004). Kuunikira kumatanthauziridwa ngati kusiyana kwa kuwerenga latency ku Kutchova Juga vs Mawu osafunikira.
Makina ochitira malonda omwe amagwiritsidwa ntchito pano ku juga za Ontario ('Cash Crop'; WMS Gaming Inc., Chicago, IL) anali woyamba kulimbikitsa. Ophunzira atha kubwereketsa ngongole ya 1–45 / spin, ndipo adauzidwa kuti alandila bonasi yofanana ndi ngongole yawo yomaliza pagawo lililonse.
Kupanikizika kwa magazi kunayesedwa ndi automatis wrist cuff (HEM-601 Omron Inc, Vernon Hills, IL).
Kusankhidwa kwa Haloperidol ngati Dopamine D2 Probe
Haloperidol (3 mg, m'kamwa) imapangitsa 60-70% D2 kulandila ndikufika pamlingo wambiri wamagazi pa 2.75 h pambuyo poyang'anira (Nordstrom et al, 1992). Mwa omwe amatsutsana ndi dopamine omwe amagwiritsidwa ntchito ndi anthu ku Canada, haloperidol (makamaka pamlingo wochepa womwe wagwiritsidwa ntchito phunziroli) ndiye amene amasankha kwambiri cholandirira cha D2. Zambiri za vitro kuchokera ku makoswe ndi maselo amunthu opangidwa (Arndt ndi Skarsfeldt, 1998; Schotte et al, 1996) akuwonetsa kuti kuyanjana kwa haloperidol kwa D2 ndikokulirapo kasanu ndi kasanu kuposa D15, cholandilira cha dopamine chomwe chimakondana kwambiri; 3-9 nthawi zazikulu kuposa -13 adrenoreceptor; ndipo 1-18 nthawi yayikulu kuposa ya serotonin 34A receptor; popanda kuyanjana kovomerezeka pamasamba ena omangiriza. Kafukufuku waumunthu wamunthu amene wamwalira (Richelson ndi Souder, 2) akuwonetsa kuyanjana pang'ono kwa -2000 adrenoreceptor (1% yaubale wa D15). Chodziwikiratu kuti mbiri yolumikizayo ndi sigma receptor, yomwe haloperidol imamangirira ndi mgwirizano wofanana ndi wolandila D2 (Schotte et al, 2). Izi zitha kuthandizira kuthana ndi kuyerekezera zinthu m'maganizo (onani Keats ndi Telford, 1996).
Kayendesedwe
Kafukufukuyu adachitika mogwirizana ndi mfundo za Helsinki Declaration (1975). Pambuyo popereka chilolezo chidziwitso, omvera adapita magawo awiri oyeserera, 1 sabata yopatula (kuti atsimikizire kutsuka), komwe adalandira 3 mg pamlomo haloperidol kapena placebo mwapangidwe wamaso awiri, wopikisana.
Pa gawo lililonse la mayeso, 2.75 h itatha dosing, maphunziro adasewera makina ogwiritsa ntchito ndi $ 200 mu ma labot yonyodola. Anatchova juga kwa 15 min kapena mpaka ngongole zawo zitatha.
ARCI ndi POMS adathandizira pa pre-kapisozi, komanso nthawi yomweyo asanafike pamakina ogwiritsa ntchito pamagetsi omwe akuyembekezeka kwambiri. Chikhumbo cha Gamble chidavotera panthawiyi komanso komanso pambuyo pa masewera a makina olowetsa. Zotsatira zosangalatsa zimayesedwa pambuyo poyeserera makina ojambula omwe amatsatiridwa nthawi yomweyo ndi Lexical Salience Task. Kuthamanga kwa magazi kunayezedwa pakatikati pa 30-min nthawi yonseyi.
Kuti muchepetse zotsalira za makina olowetsa, maphunziro amakhalabe ku labotale ya 4 h atamaliza kuyesa. Iwo adawayeza namwino wolembetsa asanachotsedwe ndikutumiza kwawo ndi taxi yolipira. Pothamangitsidwa, omvera adalandira 50-mg wa dighenhydramine (Benadryl) wosachedwa kugwiritsidwa ntchito pothana ndi vuto lakuchedwa.
Njira Yosanthula Zolemba
Zotsatira zoyeserera zinayesedwa ndi 2 (Chithandizo: Mankhwala, Placebo) 2 (Gulu: otchova njuga, owongolera) kuwunika kwa kusiyanasiyana (ANOVA). Pomwe kuli koyenera, zosintha zamkati mwa maphunziro zidaphatikizidwa mu ANOVA (mwachitsanzo, mawu mu Lexical Salience Task). Pazosintha zomwe ma pre-capsule oyambira anali kupezeka (kuwerengera kwa VAS Desire to Gamble), kusanthula kwa covariance (ANCOVA) kunachitika, pogwiritsa ntchito gawo loyambira monga kusinthasintha, kuwongolera kusiyanasiyana koyeserera ndikupatula zotsatira za Chithandizo (Wainer , 1991).
ZINTHU
Zotsatira za Capsule
Kuti awone kuyendetsa bwino kwa akhungu, kumapeto kwa maphunziro anafunsidwa kuti anene tsiku lomwe amakhulupirira kuti alandila mankhwalawo. A 2 (Gawo la Chithandizo: Mankhwala pa Gawo 1, Mankhwala pa Gawo 2) 3 (Njira Yoyankhira: Khulupirirani Tsiku 1, Khulupirirani Tsiku 2, Sindikudziwa) 2 mayankho muzitsanzo zonse anali osafunikira, 2 (df = 2, N = 20) = 2.61, p> 0.27. Ponseponse, maphunziro a 33/38 adayankhidwa 'Sindikudziwa;' awiri molondola ndipo imodzi idanenedwa molakwika Gawo 1; ndipo awiri adanenera molakwika Gawo 2. Zoyeserazo sizinasiyane ndi otchova njuga vs zowongolera, 2 <2.3, p's> 0.32, ndi lipoti limodzi lolondola mwa otchova juga, komanso amodzi owongolera. Chifukwa chake, omvera sakanatha kusankha mankhwala kuchokera ku placebo, kotero kuti kusiyana kulikonse poyankha makina olowetsa sikunali chifukwa chazomwe zimachitika chifukwa chogwiritsa ntchito mankhwala osokoneza bongo.
Gawo la 1 likuwonetsa tanthauzo (SD) la zotsatira za kapisozi pa ARCI, POMS, ndi VAS ku 2.75 h pambuyo pa dosing (kuchuluka kwa mankhwala osokoneza bongo a haloperidol) pamodzi ndi zowerengera za pre-capsule pamankhwala amtundu uliwonse mwa otchova juga komanso owongolera.
Gulu 1 - Kutanthauza (SD) Zotsatira Zapadera za Capsule (3 mg Haloperidol; Placebo) pa Peak Blood Levels (2.75 h Post-Administration) pa Sub-sikelo za ARCI, POMS (fomu yayifupi), ndi Masamba Owonetsera Analog (Zabwino / Zotsatira zoyipa; 0-10) mu Healthy Control Subjects (n = 18) ndi Pathological Gamblers (n = 20).
ARCI
A 2 (Gulu) 2 (Chithandizo) 2 (Nthawi) 7 (Subscale) ANOVA ya kuwerengera kwa ARCI kwadzetsa zotsatirazi zokhudzana ndi chithandizo: Kuyanjana kwakukulu kwa Nthawi ya Chithandizo, F (1, 216) = 5.50, p = 0.025, ndi a Kuyanjana kwakanthawi kwakanthawi kothandizirana, F (6, 216) = 2.06, p = 0.060, popanda zotsatira zina zazikulu zokhudzana ndi Chithandizo, p's> 0.50. Kuyanjana kwa Nthawi Yachithandizo kumawonetsa kuchepa kwamitundu yambiri kuchokera ku pre-capsule kupita ku post-capsule pansi pa haloperidol motsutsana ndi kuwonjezeka kwakukulu kwa zambiri kuchokera ku pre-post-capsule pansi pa placebo. Monga tawonera mu Gulu 1, kulumikizana kwakanthawi kochepa pamachitidwe akuwonetsa kusintha kwamachitidwe amitundu yaying'ono pa MBG, yomwe imakonda kukulira kuchokera ku pre-post-capsule pansi pa placebo mwa otchova njuga okha, koma idachepa onse magulu kuyambira pre-post-capsule pansi pa haloperidol. Kuwongolera kwa zotsatira ndi kukula kwakanthawi kwama Subscales osiyanasiyana ndizofanana kwambiri ndi kafukufuku wakale yemwe adayesa kuchuluka kwa 3-mg wa haloperidol mwa odzipereka athanzi (Enggasser ndi de Wit, 2001; Wachtel et al, 2002). Mphamvu yayikulu ya Gulu, F (1, 36) = 5.46, p = 0.025, ikuwonetsa kuchuluka kwakutanthauzira kwakukulu (SD), kuphatikizidwa ndi ma Subscales ndi Chithandizo, mwa otchova njuga, 3.8 (0.8), kuposa zowongolera, 3.2 (0.8 ).
POMS
A 2 (Gulu) 2 (Chithandizo) 2 (Nthawi) 6 (Subscale) ANOVA ya mavoti a POMS sanabweretse zovuta zokhudzana ndi Chithandizo, p's> 0.10.
VAS
A 2 (Gulu) 2 (Chithandizo) 2 (Subscale) ANOVA wamaphunziro a VAS adathandizira kulumikizana kwakukulu kwa Treatment Subscale, F (1, 36) = 3.44, p = 0.072, popanda zotsatira zina zofunikira zokhudzana ndi Chithandizo, p's> 0.56 . Gulu 1 likuwulula kuti zotsatirazi zikuwonetsa kuwonjezeka kochepa koma kosasintha kwa Zotsatira Zoyipa pagulu lirilonse pansi pa haloperidol vs placebo, pomwe zabwino za Zotsatira Zabwino sizinasinthe moyenera chifukwa chamankhwala.
Zotsatira za Slot Machine Game
Zodzilemba zosangalatsa zosangalatsa zamasewera
Chithunzi 1 chikuwonetsa tanthauzo (SEM) la kusangalatsidwa ndi kutchova juga, Kukondweretsedwa, ndi Kuphatikizidwa ndipo kukuwonetsa kuti haloperidol idakulitsa zochuluka pamlingo uliwonse mwa otchova juga, koma sanawoneke ngati akusintha zambiri moyenera pakuwongolera. Izi zidatsimikiziridwa ndikuwunikaku. A 2 (Gulu) 2 (Chithandizo) 3 (Subscale) ANOVA idapangitsa kuti Gulu, F (1, 36) = 6.36, p = 0.016, kulumikizana kwa Gulu la Chithandizo, F (1, 36) = 4.17, p = 0.048, ndipo palibe zotsatira zabwino kwambiri, p's> 0.50. Zomwe gulu limachita zimawonetsa zambiri pamasewera otchova juga kuposa zowongolera pama Subscales and Therapy. Kuyanjana kukuwonetsa kuwonjezeka kwakukulu kwa kuchuluka kwa Subscale pansi pa haloperidol mwa otchova njuga koma osawongolera; ndipo kuchepa kwa zotsatira zakukwera kwakukulu kumawonetsa kuti haloperidol idakhala ndi mphamvu yowonjezerapo pama subscales onse atatu. Kutanthauzira komwe kumatanthauza kugawidwa kwa ma subscales atatu anali r2 = 0.66, kwa otchova njuga, ndi r2 = 0.65, pakuwongolera. Chifukwa chake, chisangalalo chodziwika bwino pamasewerawa chimakhala pafupifupi magawo awiri mwa atatu amasiyana pamasamba ang'onoang'ono, pomwe pafupifupi gawo limodzi mwamagawo atatu anali osiyana ndi gawo lililonse.
Chithunzi 1.
Kutanthauza (SEM) komwe kunadzetsa chisangalalo pamasewera osanja a 15-min pamasewera olamulira athanzi (n = 18) ndi otchova njuga (n = 20) pansi pa haloperidol (3 mg, m'kamwa) ndi placebo. * Mankhwala osokoneza bongo, p <0.001.
Chodziwonetsa chokha chokhudza kutchova juga
Chithunzi 2 chikuwoneka chimatanthawuza (SEM) Kukhumba Miyezo ya Gamble isanachitike komanso pambuyo pa masewera a makina osewerera. Chiwonetserochi chikuwonetsa kuti haloperidol pakokha idalibe zotsatira za Desire Game Zokhumba zofunikira zimakwera kuchokera pa pre-to-post-masewera pansi pa placebo pagulu lirilonse; ndipo kuchuluka kwa chiwonetsero cha masewerawa kunawoneka kukhala kokulirapo pansi pa haloperidol mu otchova juga koma osawongolera. Amasanthula izi.
Chithunzi 2.
Kutanthauza (SEM) komwe akuti adafuna kutchova juga asanakwane kapena pambuyo pa masewera a 15-min pamakina owongolera athanzi (n = 18) ndi otchovera njuga (n = 20) pansi pa haloperidol (3 mg, m'kamwa) ndi placebo. * Mankhwala osokoneza bongo, p <0.001.
Chiyambi cha 2 (Gulu) 2 (Chithandizo) ANOVA yamanambala a pre-capsule Desire (osawonetsedwa) adatulutsa gawo lalikulu la Gulu, F (1, 36) = 38.39, p <0.001, ndipo palibe zotsatira zina zofunikira, p's> 0.26, yowonetsa chikhumbo choyambirira (SD) choyambirira cha kapisozi pachikhumbo cha otchova njuga, 3.6 (1.8) kuposa zowongolera, 0.4 (1.8) pagawo lililonse loyesa. Kupatula zotsatira za Chithandizo (Wainer, 1991), 2 (Gulu) 2 (Chithandizo) 2 (Pre-Post Game) ANCOVA ya Desire to Gamble zambiri zinkachitika pogwiritsa ntchito pre-capsule Desire alama monga momwe zimasinthira. ANCOVA idapereka kulumikizana kwakukulu m'njira zitatu, F (1, 35) = 4.21, p = 0.048, ndi zotsatira zoyambira m'mbali za Gulu, p = 0.056, kuwonetsa kuchuluka kwa otchova juga kuposa owongolera.
Kusanthula kosavuta kunapeza kuti panalibe vuto lililonse la Chithandizo pa chisanachitike masewera a otchova juga kapena owongolera, p's> 0.50. Pansi pa placebo, masewerawa adakulitsa chidwi cha otchova njuga, t (35) = 6.31, p <0.001, ndikuwongolera, t (35) = 3.90, p <0.001. Pansi pa haloperidol, kuwonjezeka kwa chikhumbo chisanachitike pambuyo pake kunakulitsa kutchova juga, t (35) = 4.13, p <0.001, koma osati pakuwongolera, p> 0.50. Chifukwa chake, haloperidol idalimbikitsa zomwe zimayambitsa masewera pamakina otchovera njuga.
Kukhazikitsa kwa ma seantic amanjenje: lexical salience task
Gawo la 2 likufotokoza tanthauzo (SD) nthawi yowerengera (RT; ms) kuchuluka kwa mawu a Kutchova Njuga ndi Nutral komanso zikhalidwe zamagama a Ancillary pa Lexical Salience Task yowongolera ndi kutchova njuga pansi pa Chithandizo chilichonse. Tebulo likuwonetsa kuti, pagulu lirilonse, RT inali yochepetsetsa kwambiri kumawu a Neutral kuposa mitundu ina yonse yamawu pansi pa placebo ndi haloperidol. Monga tanena kale, kusiyana kwa RT ku gulu la mawu osavomerezeka kukugwirizana ndi mawu osavomerezeka a Neutral omwe amayeza malo; kuphatikiza kwakukulu, (Chosavomerezeka cha Neutral), ndizokulirapo.
Gulu 2 - Kutanthauza (SD) Nthawi Yoyankha Kuwerenga (ms) ya Word Stimuli pa Lexical Salience Task Under Placebo ndi Haloperidol (3 mg) mu Healthy Control Subjects (n = 18) ndi Pathological Gamblers (n = 20).
Gome lonse
A 2 (Gulu) 2 (Chithandizo) 5 (Chikhalidwe cha Mawu) ANOVA idapereka kulumikizana kwakukulu m'njira zitatu, F (4, 144) = 3.00, p = 0.021. Zotsatira zosavuta zowunikira zowongolera zidapeza kuti kusiyana kwa RT kuchokera ku Neutral pansi pa mankhwala vs placebo sikunasinthe kwambiri pamawu a Njuga, p> 0.06; yowonjezera mawu Amowa, t (144) = 7.50, p <0.001; ndi kuchepa kwa onse Positive, t (144) = 7.91, p <0.001, ndi Negative Afact mawu, t (144) = 11.08, p <0.001. Chifukwa chake, pakuwongolera, mawu otchova juga sanali oyenera kugwiritsa ntchito mankhwala osokoneza bongo kuposa placebo; Mawu amowa anali odziwika kwambiri pamankhwala osokoneza bongo, ndipo mawu okhudzidwa, mosasamala kanthu za valence, anali ocheperako chifukwa chogwiritsa ntchito mankhwala osokoneza bongo. Kuyendera kuchuluka kwa zowongolera mu Gulu 2 zikuwonetsa kuti, pansi pa placebo, RT ku Mowa mawu anali ochedwa modabwitsa poyerekeza ndi mawu ena olimbikitsa. Chifukwa chake, kusiyana kwakukulu pakati pa RT ndi Mowa motsutsana ndi mawu osalowerera omwe ali pansi pa haloperidol m'maphunzirowa atha kuwonetsa kuponderezana ndi tanthauzo.
Kuyendera kuchuluka kwa ma RT kwa otchova juga m'mawu osiyanasiyana osalowerera Ndale pansi pa placebo kuwulula kuti onse anali ofanana. Kusanthula kosavuta kwa otchova njuga kunapeza kuti haloperidol idakulitsa kwambiri kusiyana kwa RT kuchokera ku Neutral ya Mawu Kutchova Juga, t (108) = 2.91, p <0.01; ndi mawu Olimbikitsa Amakhudzidwa, t (108) = 5.26, p <0.001; koma sanasinthe RT yofanana ndi mitundu ina ya mawu, p's> 0.50. Chifukwa chake, zotsatira za otchova juga zikuwonetsa kuti mawu a Kutchova Juga ndi Mawu Olimbikitsa Amakhudzidwa anali ofunika kwambiri pansi pa haloperidol kuposa placebo.
Zokhudza thupi: systolic magazi
Chithunzi 3 chikuwonetsa zotsatira za masewerawa pamakina pama systolic magazi (mmHg) pansi pa haloperidol ndi placebo muzowongolera. Chithunzi 4 chikuwonetsa zambiri zogwirizana ndi otchova juga. Ziwerengerozi zikuwonetsa kuti, pansi pa placebo, kuthamanga kwa magazi kunakwera kuchokera masewera asanafike masewera am'mbuyomu m'magulu onse awiri. Kuphatikiza apo, m'magulu onse awiri, kuchuluka-komwe kumayambitsa kuthamanga kwa magazi kunali kwakukulu kwambiri pansi pa haloperidol. Izi ziwunikiridwa ndi kusanthula.
Chithunzi 3.
Kutanthauza (SEM) systolic magazi (mm Hg) poyambira chisanachitike kapisolo komanso panthawi ya 30 mphindi isanachitike komanso pambuyo pa masewera a makina a 15-min slot mumaphunziro olamulira athanzi (n = 18) under haloperidol (3 mg, oral) ndi placebo .
Chithunzi chokwanira ndi nthano (15K)
Chithunzi 4.
Kutanthauza (SEM) systolic magazi (mm Hg) poyambira chisanachitike kapisolo komanso panthawi ya 30 min isanachitike komanso pambuyo pa masewera a makina a 15-min slot in gologicaller (n = 20) under haloperidol (3 mg, oral) ndi placebo.
A 2 (Gulu) 2 (Chithandizo) 8 (Nthawi Yoyesa) ANOVA wama systolic magazi amatulutsa nthawi yayitali yothandizira, F (7, 252) = 2.64, p = 0.012, komanso kulumikizana kwakukulu m'njira zitatu, F (Matshi 7, 252) = 2.89, p = 0.006. Kuyanjana kwa njira ziwirizi kumawonetsa kuwonjezeka kosasintha pazotsatira za Nthawi (masewera atatha masewera asanachitike) pansi pa haloperidol vs placebo pakuwongolera, t (252) = 6.15, p <0.001, komanso otchova njuga, t (252) = 5.16, p <0.001. Kulumikizana kwa njira zitatu kumawonetsa kusiyana kwamagulu munthawi yomwe masewera asanakwane amasewera pachithandizo chilichonse. Pakulamulira, kuthamanga kwa magazi kocheperako kunachitika mphindi 30 isanayambike makina olowetsa pansi pa placebo komanso masewera asanakwane haloperidol; mwa otchova juga njirayi idasinthidwa, pomwe masewera asanakwane amachitika masewera asanakwane pansi pa placebo, koma mphindi 30 masewera asanakwane pansi pa haloperidol. Makamaka, haloperidol idakulitsa kuwonjezeka kwa kuthamanga kwa magazi pamlingo wofanana m'magulu onsewa. Khalidwe labetcha mumasewera amakina oyeserera Mndandanda wa 2 2 ANOVA amachitidwe pakubetcha mumasewera a makina oyeserera (amatanthauza kubetcha potembenuka, kubetcherana pazambiri pamalipiro, ngongole zomaliza zomwe amapeza) sizinabweretse zovuta zokhudzana ndi Chithandizo, p's> 0.25. Zotsatira zazikuluzikulu zinali zoyambitsa zazikulu za Gulu la mean (SD) yathunthu yama spins / masewera, omwe anali ambiri mwa otchova njuga, 89.4 (39.4) kuposa owongolera, 60.6 (41.6), F (1, 36) = 9.57, p = 0.004.
KUKANGANANI
Haloperidol, palokha, inalibe zotsatira zakusiyasiyana kwa otchova njuga komanso kuwongolera moyenera pazomwe zimachitika pakumwa mankhwala osokoneza bongo monga kuyesedwa ndi ARCI, POMS, ndi milingo ya VAS. M'magulu onse awiriwa, panali zotsatira zoyipa zazing'ono pa subscale ya ARCI MBG (idatsika ndikukhalanso bwino) komanso pamlingo wa VAS Bad Zotsatira zomwe zinali zogwirizana ndi zovuta zomwe zimachitika chifukwa cha mankhwala a neuroleptic. Ponseponse, kapangidwe kake ndi kuchuluka kwa masukulu ndi makulidwe amakulidwe anali ofanana kwambiri ndi omwe adafotokozedwa m'maphunziro am'mbuyomu pogwiritsa ntchito mlingo womwewo mwa odzipereka athanzi labwino (Enggasser and de Wit, 2001; Wachtel et al, 2002).
Ganizirani kaye za zomwe otchova njuga amapeza, haloperidol idalimbikitsa zotsatira zosangalatsa zamasewera makina opanga monga momwe zimasangalalira ndi Kusangalala, Kusangalala, ndi Mulingo wothandizira. Kutanthauza kosagwirizana pakati pamaseweredwe atatu anali R2 = 0.66, kwa otchova juga, kuwonetsa kuti chisangalalo wamba chamasewera chimakhala pafupifupi gawo limodzi mwa magawo atatu atatu a kusiyana mumagawo ang'onoang'ono, pomwe gawo limodzi mwa magawo atatu aliwonse kusiyanasiyana kunali kwapadera pachigawo chilichonse.
Haloperidol paokha idalibe phindu lililonse pakhumbo la Pre-Gire pa Masewera olimbana ndi otchova njuga. Pansi pa placebo, makina a slot makina adakulitsa Kukhumba Kwa Gambule ndi haloperidol adakulitsa kwambiri zotsatira zabwino zaotchova juga. Chifukwa chake, haloperidol inali ndi zotsatirapo zopindulitsa komanso zopatsa chidwi pamasewera olimbitsa makina, njira yomwe imatsimikizira mitundu iwiri ya indices. Haloperidol inapititsanso ulesi wa mawu a Kutchova Njuga okhudzana ndi mawu a Nutral, monga zikuwonetsedwa ndi mayankho owerenga mwachangu pa Lexical Salience Task. Pokhudzana ndi kuyendetsa thupi. makina owongolera adatsogolera kuwonjezeka kwakukulu kwa kuthamanga kwa magazi pansi pa placebo ndi haloperidol kwambiri kunapangitsa izi. Chifukwa chake, haloperidol inakulitsa phindu, priming, komanso zolimbitsa thupi chifukwa cha kutchova juga kwa otchova njuga. Zotsatira zinali zowonekera komanso zosinthika pazodzilemba nokha, mayankho owerengera, komanso mayendedwe a magazi.
Zotsatira zingapo zowongolera zinali zogwirizana ndi za otchova njuga. Choyamba, pakuwongolera, haloperidol paokha idalibe phindu lililonse pa Chikhumbo cha Pre-Gutle. Chachiwiri, pansi pa placebo, makina osewerera amakina adakonzera Desire Gamble ndikuwonjezera kuthamanga kwa magazi pamaulamuliro. Kupeza komaliziraku kumagwirizana ndi zomwe zadziwika kale za mayankho apamwamba achifundo a adrenal pamavuto komanso osagwirizana ndi vuto lotchova juga pa kasino (Meyer et al, 2004). Pomaliza, haloperidol inathandizira zotsatira zamphamvu za masewerowo pakuwongolera ndi kuchuluka kwa mankhwalawo anali ofanana ndendende ndi omwe amatchova juga.
Mosiyana ndi otchova juga, kuwongolera, haloperidol sikunawonetsetse phindu pamasewerawa, adalimbikitsa chidwi chofuna kutchova njuga kapena kuyambiranso kuyankhula mawu a Kutchova Njuga pa Lexical Salience Task. Chifukwa chake, pamalamulo olamulira omwe sanali otchova juga, kupititsa patsogolo ntchito kwa haloperidol kumapangitsa kuti azikhala osayanjanitsidwa ndi zotsatira zake pamachitidwe oyankha opindulitsa pa njuga. Komabe, akatswiri olamulira adawoneka kuti akupeza makina osewerera kuti azikhala olimbitsa, monga akuwonetsedwa ndi zotsatira zosangalatsa za masewerawo komanso kuyambitsa kwa Desire mpaka Gamble komwe kunayambitsa masewera. Sizikudziwika bwino chifukwa chomwe zimapangitsa kuti mayanjano akhale osagwirizana ndi zotsatira za haloperidol pazolimbitsa thupi komanso mphotho yolipira pamagetsi osagwiritsa ntchito njuga. Izi zimadzutsa funso loti momwe haloperidol ingakhudzire otchova juga munjira yoyeserayi. Ndizotheka kuti mbiri yakutchova njuga komanso mayankho olumikizana kapena kulolerana kumatha kuyambitsa zotsatira za haloperidol pakulimbikitsa njuga. Pali umboni wina pakufufuza ndi nyama kuti dopamine system ndi D2 receptor makamaka imagwira mbali ina pakulimbikitsa kwamphamvu kwa zomwe zimapangitsa kuti zizikhala ndi chidwi ndi zomwe sizimagwirizana ndimawu (cf. Dockstader et al, 2001).
Kupeza kuti gawo la D2 blockade lidakulitsa zotsatira zabwino za kutchova juga kwa otchova juga kwazomwe zitha kuoneka ngati zodabwitsa. Poganizira kufanana pakati pa mitsempha pakati pa juga ndi kulimbikitsidwa kwa psychostimulant (Zack ndi Poulos, 2004), kafukufuku pazotsatira za dopamine antagonists pa psychostimulant mphotho ndizoyenera.
Kafukufuku wowonjezereka ndi zinyama pogwiritsa ntchito mitundu yosiyanasiyana yazida wapeza kuti D2 blockade mosalekeza imachepetsa mphamvu yowonjezera ya psychostimulant mankhwala (Amit ndi Smith, 1992; Bari ndi Pierce, 2005; Britton et al, 1991; Caine et al, 2002; Fletcher, 1998).
M'maphunziro ndi anthu, zotsatira za otsutsana ndi D2 pamphotho ya psychostimulant zakhala zikugwirizana. Maphunziro ena sanapeze zotsatira (mwachitsanzo, Brauer ndi de Wit, 1997; Wachtel et al, 2002); ena adapeza atatsitsa mphoto ya psychostimulant (mwachitsanzo Gunne et al, 1972; Jonsson, 1972; Sherer et al, 1989); ndipo kafukufuku m'modzi wapeza mphoto yowonjezereka ya psychostimulant (Brauer ndi de Wit, 1996). Pakuunika kwawo kwa zolemba zama psychostimulant, a Brauer et al (1997) amakambirana za kuwoneka kosowa kwa kulemberana makalata pakati pa nyama ndi kafukufuku wamunthu potengera dosing yogwira ntchito komanso kusiyanasiyana kwa njira. Pakuwona izi, kuwunika kwa mayendedwe a mlingo wa haloperidol pakulimbikitsa kutchova juga kungapangitse kuwonjezereka kwa kufunsa kwatsopano.
Umboni wochokera ku maphunziro apamwamba, komabe, zikuwoneka kuti zikugwirizana ndi zomwe zapezeka pano kwa otchova njuga. M'maphunziro angapo, Volkow et al (1999, 2000) adapeza kuti kupezeka kwapansi kwa D2 receptor kunali kosakanikirana ndi zotsatira zabwino zopindulitsa za psychostimulant, methylphenidate mu odzipereka athanzi. Mwanjira ina, kutsika kupezeka kwa ma D2 receptors, kwakukulu kunali kokonda mankhwala. Komanso, monga tafotokozera m'mbuyomu, zomwe zapezazi zikufanana ndi zomwe zinali 'zoyambitsa' kupeza kuti chithandizo choyambirira ndi 1- kapena 2-mg wa wotsutsana ndi D2, pimozide idakulitsa kusankhana komanso 'kukonda' mlingo wa 20-mg wa d- amphetamine mwa odzipereka (Brauer ndi de Wit, 1996).
Chosangalatsa ndichakuti, mu kafukufuku wina, Volkow et al (2003) adapeza kuti kuwonjezeka kwa methylphenidate komwe kumayambitsa kuthamanga kwa magazi kumalumikizidwa kwambiri ndi plasma epinephrine komanso kuwonjezeka kwa striatal dopamine. Adanenanso kuti zovuta zamagetsi za methylphenidate zimayanjanitsidwa ndi kuwonjezeka kwa DA mu zotumphukira za epinephrine. Nkhaniyi ikubweretsa kuthekera kwakuti kukwera kwa juga komwe kumayambitsa kuthamanga kwa magazi pansi pa haloperidol mu kafukufuku wapanoyu mwina kukuwonetsa kukwezeka kwa striatal dopamine ndi zotsatira zofananira pa epinephrine.
Monga taonera kumayambiriro, Kafukufuku wamtundu wapereka umboni wogwirizana wosonyeza kuti ntchito yochepa ya D2 receptor ndi chiopsezo chofunikira kwambiri pakukula kwa njuga zamatenda (Comings et al, 1996). Kafukufuku wotsatira wa fMRI ndi odzipereka athanzi adapeza kuti iwo omwe ali ndi majini (A1 alile) omwe ali olumikizidwa ndi ntchito yochepa ya D2 receptor adawonetsa kupititsa patsogolo mphotho zomwe zikuyembekezeredwa pamagawo ofunikira muubongo panthawi yogwirira ntchito njuga (Cohen et al, 2005).
Zomwe zapezedwa pano zikuwonjezera kufunsa uku pogwiritsa ntchito njira yowerengera mankhwala kuti iwonetsetse kuti kupezeka kwapansi kwa D2 komwe kumapangidwa ndi mankhwala kumathandizira zotsatira zolimbikitsa za kutchova njuga kwa makina a slot. Zotsatira izi zikugwirizana ndi zomwe zapeza bwino zomwe zanenedwa pamwambapa, ndipo zimapereka umboni woyesera pakati pa ubale wamalingaliro a neurochemical-womwe ungapangitse kuyanjana pakati pa osagwirizana mumtundu wa D2 receptor ndikuyika pachiwopsezo cha juga ya pathological.
Potengera kufanana kwa mitsempha pakati pa kutchova juga ndi psychostimulant Kulimbitsa (Zack ndi Poulos, 2004), zomwe zapezeka zikuwonetsa kuti magawo ena a dopamine omwe amasinthidwa ndi D2 ndikuwonjezera kulimbikitsa kwa psychostimulant, mwachitsanzo, D1 ndi D3 receptors (Xu, 1998), khalani ofunikira pakulimbikitsa kutchova juga. Pomaliza, zomwe zapezeka pano zikuonetsa kuti mankhwala omwe amalimbikitsa kufalitsa kwa dopamine pamalo ochezera a D2 atha kukhala akuwalonjeza ofuna kuti akafufuze mankhwala a juga ya pathological.
Zothandizira
1. Amit Z, Smith BR (1992). Remoxipride, wogwirizira wapadera wa D2 dopamine: kuwunika kwake kodzisamalira payekha komanso zotsatira zake pa d-amphetamine payekha. Pharmacol Biochem Behav 41: 259-261.
2. Arndt J, Skarsfeldt T (1998). Kodi ma antipsychotic akumwa ali ndi machitidwe amomwewo pamapangidwe apamwamba? Kuunikiranso umboniwo. Neuropsychopharmacology 18: 63-101.
3. Bari AA, Pierce RC (2005). D1-ngati ndi D2 dopamine receptor antagonists omwe amapatsidwa gawo la zigawo za zigawo za maukono amachepetsa cocaine, koma osati chakudya, cholimbitsa. Neuroscience 135: 959-968.
4. Beaudoin CM, Cox BJ (1999). Makhalidwe azovuta kutchova juga munkhani yaku Canada: kafukufuku woyambirira pogwiritsa ntchito mafunso omwe ali ndi DSM-IV. Kodi J Psychiatry 44: 483-487.
5. Beck AT, Beck RW (1972). Kuyang'ana odwala omwe ali ndi mavuto m'mabanja. Njira yofulumira. Postgrad Med 52: 81-85.
6. Blum K, Sheridan PJ, Wood RC, Braverman ER, Chen TJ, Comings DE (1995). Mitundu ya Dopamine D2 receptor mitundu: mayanjano ndi kuphatikiza maphunziro mu malingaliro osalimbikitsa-owonjezera-okakamiza. Pharmacogenetics 5: 121–141.
7. Blum K, Sheridan PJ, Wood RC, Braverman ER, Chen TJ, Cull JG et al (1996). Mtundu wa D2 dopamine receptor monga chosankha cha kuchepa kwa mphotho. JR Soc Med 89: 396-400.
8. Brauer LH, de Wit H (1996). Kuyankha kogwirizana ndi d-amphetamine yekha komanso pambuyo pimozide onyentchera mwa nthawi zonse, athanzi odzipereka. Psychology 39: 26–32.
9. Brauer LH, de Wit H (1997). Mulingo wamphamvu pimozide satsekera amphetamine-anachititsa euphoria mwa odzipereka odzipereka. Pharmacol Biochem Behav 56: 265-272.
10. Brauer LH, Goudie AJ, de Wit H (1997). Dopamine ligands ndi zolimbikitsa zomwe zimachitika amphetamine: mitundu ya zinyama motsutsana ndi deta ya anthu yothandizira. Psychopharmacology 130: 2–13.
11. Britton DR, Curzon P, Mackenzie RG, Kebabian JW, Williams JE, Kerkman D (1991). Umboni wokhudzidwa ndi ma receptor onse a D1 ndi D2 pokonzanso cocaine payekha. Pharmacol Biochem Behav 39: 911-915.
12. Caine SB, Negus SS, Mello NK, Patel S, Bristow L, Kulagowski J et al (2002). Ntchito za dopamine D2-ngati zolandilira mu cocaine wodziyendetsa: maphunziro ndi mbewa za D2 receptor mutant ndi buku la D2 receptor antagonists. J Neurosci 22: 2977-2988.
13. Cohen MX, Young J, Baek JM, Kessler C, Ranganath C (2005). Kusiyana kwamwini pakuwonjezera komanso dopamine genetics kulosera mayankho a mphotho ya neural. Brain Res Cogn Brain Res 25: 851-861.
14. Comings DE, Rosenthal RJ, Lesieur HR, Rugle LJ, Muhleman D, Chiu C et al (1996). Kafukufuku wa dopamine D2 receptor gene mu njuga zamatenda. Pharmacogenetics 6: 223–234.
15. Dockstader CL, Rubinstein M, Grandy DK, Low MJ, van der Kooy D (2001). Rec2or ya D13 ndiyofunikira kwambiri pakuyendetsa zolinga za opiate kokha mu mbewa za opiate komanso zodalira. Eur J Neurosci 995: 1001-XNUMX.
16. Enggasser JL, de Wit H (2001). Haloperidol amachepetsa chowonjezera ndi kulimbikitsa zotsatira za Mowa mu zakumwa zakumwa. Mowa Clin Exp Res 25: 1448-1456.
17. Fletcher PJ (1998). Kuyerekezera kwa zotsatira za risperidone, raclopride, ndi ritanserin pakudziyendetsa pakokha kwa d-amphetamine. Pharmacol Biochem Behav 60: 55-60.
18. Chisomo AA (2000). Mitundu ya tonic / phasic model ya dopamine system regulation ndi tanthauzo lake kumvetsetsa mowa komanso kukhumba kwa psychostimulant. Zowonjezera 95 (Suppl 2): S119-S128. | Nkhani | PubMed | ISI |
19. Gunne LM, Anggard E, Jonsson LE (1972). Ziyeso zamankhwala ndi mankhwala amphetamine-blocking. Psychiatr Neurol Neurochir 75: 225–226.
20. Haertzen CA (1965). Adiction Research Center Inventory (ARCI): Kukula kwa chiwopsezo cha mankhwala ambiri. J Nerv Ment Dis 141: 300-307.
21. Heinz A, Siessmeier T, Mlembi J, Hermann D, Klein S, Grusser SM et al (2004). Mgwirizano pakati pa dopamine D (2) zolandilira mu ventral striatum ndi mkati kukonzanso zakumwa zoledzeretsa ndikukhumba. Am J Psychiatry 161: 1783-1789.
22. Jonsson L (1972). Pharmacological blockade ya amphetamine zotsatira zimadalira amphetamine. Eur J Clin Pharmacol 4: 206-211.
23. Keats AS, Telford J (1964). Omwe amatsutsa a Narcotic monga analgesics. Zokhudza matenda. Mu: Gould RF (ed) Module Modform in Drug Design, Advances in Chemistry, Series 45. American Chemical Society: Washington, DC. masap. 170-176.
24. Meyer G, Schwertfeger J, Exton MS, Janssen OE, Knapp W, Stadler MA et al (2004). Kuyankha kwa Neuroendocrine pa kutchova juga kwa kasino mu otchova njuga. Psychoneuroendocrinology 29: 1272–1280.
25. Morasco BJ, Vom Eigen KA, Petry NM (2006). Kukula kwa kutchova njuga kumalumikizidwa ndi thanzi lakuthupi komanso kwamaganizidwe mu odwala oyang'anira chithandizo cham'mizinda chachikulu. Gen Hosp Psychiatry 28: 94-100.
26. Nader MA, Czoty PW (2005). Kulingalira kwa PET kwa dopamine D2 zolandila mu mitundu yosiyanasiyana ya nkhanza: cidziwitso cha chibadwa chotsutsana ndi chilengedwe. Am J Psychiatry 162: 1473-1482.
27. Noble EP (2000). Zowonjezera ndi njira yake yolipira kudzera ma polymorphisms a D2 dopamine receptor gene: kuwunika. Eur Psychiatry 15: 79-89.
28. Nordstrom AL, Farde L, Halldin C (1992). Nthawi ya D2-dopamine zolandilira kulowetsedwa ndi PET pambuyo limodzi Mlingo wa haloperidol. Psychopharmacology 106: 433-438.
29. Reuter J, Raedler T, Rose M, Dzanja I, Glascher J, Buchel C (2005). Kutchova njuga kwachikhalidwe kumalumikizidwa ndikuyambitsa kuchepa kwa machitidwe a mesolimbic mphotho. Nat Neurosci 8: 147–148.
30. Richelson E, Souder T (2000). Kumangirira kwa mankhwala a antipsychotic kwa olandila ubongo wa anthu kumangoganiza zopangidwa zatsopano. Moyo Sci 68: 29–39.
31. Scherrer JF, Xian H, Shah KR, Volberg R, Slutske W, Eisen SA (2005). Zotsatira zamtundu, chilengedwe, komanso zovuta zapakati pa moyo wamunthu zomwe zimachitika paumoyo wokhudzana ndiumoyo pamavuto ndi otchovera njuga. Arch Gen Psychiatry 62: 677-683.
32. Schotte A, Janssen PF, Gommeren W, Luyten WH, Van Gompel P, Lesage AS et al (1996). Risperidone poyerekeza ndi mankhwala atsopano a antipsychotic atsopano ndi omasulira: mu vitro ndi vivo receptor. Psychopharmacology 124: 57-73.
33. Self DW, Stein L (1992). Receptor subtypes mu opioid ndi mphotho yothandizira. Pharmacol Toxicol 70: 87-94.
34. Shacham S (1983). Mtundu wofupikitsidwa wa Mbiri ya Mood States. J Pers Onani 47: 305-306.
35. Sherer MA, Kumor KM, Jaffe JH (1989). Zotsatira za intravenous cocaine zimasinthidwa pang'ono ndi haloperidol. Psychology Res 27: 117–125.
36. Volkow ND, Chang L, Wang GJ, Fowler JS, Ding YS, Sedler M et al (2001). Otsika otsika a ubongo dopamine D2 receptors mu methamphetamine abusers: mayanjano ndi metabolism mu orbitof mbeleal cortex. Am J Psychiatry 158: 2015-2021.
37. Volkow ND, Fowler JS, Wang GJ (2004). Ubongo wamunthu womwe umawonetsedwa powunikira maphunziro: Neuropharmacology 47 (Suppl 1): 3–13.
38. Volkow ND, Fowler JS, Wolf AP, Schlyer D, Shiue CY, Alpert R et al (1990). Zotsatira zakuzunza koopsa kwa cocaine pa postynaptic dopamine receptors. Am J Psychiatry 147: 719-724.
39. Volkow ND, Wang GJ, Fowler JS, Logan J, Gatley SJ, Gifford A et al (1999). Kuneneratu kwa kulimbitsa mayankho kuma psychostimulants mwa anthu mwa kuchuluka kwa ubongo wa dopamine D2 receptor. Am J Psychiatry 156: 1440-1443.
40. Volkow ND, Wang GJ, Fowler JS, Logan J, Hitzemann R, Ding YS et al (1996). Amatsika mu ma dopamine receptors koma osati oyendetsa dopamine mu zidakwa. Mowa Clin Exp Res 20: 1594-1598.
41. Volkow ND, Wang GJ, Fowler JS, Molina PE, Logan J, Gatley SJ et al (2003). Zochitika mu mtima za methylphenidate mwa anthu zimagwirizana ndi kuwonjezeka kwa dopamine mu ubongo ndi epinephrine mu plasma. Psychopharmacology 166: 264-270.
42. Volkow ND, Wang GJ, Fowler JS, Thanos PP, Logan J, Gatley SJ et al (2002). Bept DA D2 receptors amalosera zolimbitsa zotsatira za zopatsa mphamvu mwa anthu: kuwerengetsa kubwereza. Synfall 46: 79-82.
43. Volkow ND, Wang GJ, Telang F, Fowler JS, Logan J, Childress AR et al (2006). Cocaine cates ndi dopamine mu dorsal striatum: limagwirira ntchito kukhumba cocaine. J Neurosci 26: 6583-6588.
44. Wachtel SR, Ortengren A, de Wit H (2002). Zovuta za pachimake haloperidol kapena risperidone pazomwe zimayankhidwa kwa methamphetamine mu odzipereka athanzi. Kumwa Mowa Mankhwala 68: 23–33.
45. Wainer H (1991). Kusintha kwamitengo yosiyanasiyana: Chodabwitsanso cha Ambuye. Buluu wa Psychol 109: 147-151.
46. Wang GJ, Volkow ND, Fowler JS, Logan J, Abumrad NN, Hitzemann RJ et al (1997). Dopamine D2 receptor kupezeka muzinthu zomwe zimadalira opiate isanachitike komanso atatha kudzipatula. Neuropsychopharmacology 16: 174-182.
47. Wang GJ, Volkow ND, Logan J, Pappas NR, Wong CT, Zhu W et al (2001). Ubongo dopamine ndi kunenepa kwambiri. Lancet 357: 354–357.
48. Xu M (1998). Kutsegula dopamine D3 receptor ntchito poyankha psychostimulants pogwiritsa ntchito majini. Ann NY Acad Sci 844: 27–39.
49. Zack M, Poulos CX (2004). Amphetamine amalimbikitsa kulimbikitsa kutchova njuga ndi ma intaneti okhudzana ndi njuga pamagetsi ovuta. Neuropsychopharmacology 29: 195–207.
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