Department of Psychiatry, College of Physicians and Surgeons of Columbia University and Division on Substance Abuse, New York State Psychiatric Institute, 1051 Riverside Drive, New York, NY 10032, USA.
Psychopharmacology (Berl). 2011 Aug;216(3):379-87. doi: 10.1007/s00213-011-2231-6. Epub 2011 Mar 5.
Partial dopamine receptor agonists have been proposed as candidate pharmacotherapies for cocaine dependence.
This 42-day, within-subject, human laboratory study assessed how maintenance on aripiprazole, a partial D(2) receptor agonist, influenced smoked cocaine self-administration, cardiovascular measures, subjective effects, and cocaine craving in nontreatment-seeking, cocaine-dependent volunteers.
In order to achieve steady-state concentrations, participants (n = 8 men) were administered placebo and aripiprazole (15 mg/day) capsules in counter-balanced order for 21 days. A smoked cocaine dose-response curve (0, 12, 25, 50 mg) was determined twice under placebo and aripiprazole maintenance. Sessions comprised a "sample" trial, when participants smoked the cocaine dose available that session, and five choice trials, when they responded on a progressive-ratio schedule of reinforcement to receive the cocaine dose or receive $5.00.
Cocaine's reinforcing, subjective, and cardiovascular effects were dose-dependent. Aripiprazole significantly increased cocaine (12, 25 mg) self-administration. Following a single administration of cocaine (25 mg), aripiprazole decreased ratings of how much participants would pay for that dose. Following repeated cocaine (50 mg) self-administration, aripiprazole decreased ratings of cocaine quality, craving, and good drug effect as compared to placebo.
These data suggest that aripiprazole may have increased self-administration to compensate for a blunted subjective cocaine effect. Overall, the findings do not suggest aripiprazole would be useful for treating cocaine dependence.
部分多巴胺受体激动剂已被提议作为可卡因依赖的候选药物治疗。
这项为期 42 天、在受试者内进行的人体实验室研究评估了阿立哌唑（一种部分 D2 受体激动剂）维持治疗如何影响非治疗寻求的可卡因依赖志愿者的吸烟可卡因自我给药、心血管测量、主观效应和可卡因渴求。
为了达到稳态浓度，参与者（n=8 名男性）以平衡的顺序接受安慰剂和阿立哌唑（15mg/天）胶囊，持续 21 天。在安慰剂和阿立哌唑维持治疗下，两次确定了吸烟可卡因剂量反应曲线（0、12、25、50mg）。在“样本”试验中，参与者吸烟了当时可获得的可卡因剂量，在五次选择试验中，他们根据强化递增比率的方案对可卡因剂量或获得 5 美元进行反应。
可卡因的强化、主观和心血管效应是剂量依赖性的。阿立哌唑显著增加了可卡因（12、25mg）的自我给药。单次给予可卡因（25mg）后，阿立哌唑降低了参与者愿意支付该剂量的评分。与安慰剂相比，在反复给予可卡因（50mg）后，阿立哌唑降低了对可卡因质量、渴求感和良好药物效果的评分。
这些数据表明，阿立哌唑可能增加自我给药以弥补主观可卡因效应的减弱。总体而言，研究结果表明阿立哌唑不太可能对治疗可卡因依赖有用。
