Effects of ecopipam, a selective dopamine D1 antagonist, on smoked cocaine self-administration by humans
Effects of ecopipam, a selective dopamine D1 antagonist, on smoked cocaine self-administration by humans
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DOI：
10.1007/s002130100725
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发表时间：
2001-06-01
影响因子：
3.4
通讯作者：
Fischman, MW
中科院分区：
文献类型：
--
作者：
Haney, M;Ward, AS;Fischman, MW
基本原理：在实验室动物和人类中获得的数据表明，多巴胺DI受体拮抗剂减少可卡因自我给药，并阻断可卡因的辨别刺激和主观效应。目的：本研究探讨了选择性多巴胺D1拮抗剂ecopipam（SCH 39166）对人体可卡因强化、心血管和主观效应的影响。研究方法：10名非寻求治疗的可卡因吸烟者（2名女性，8名男性），居住在住院研究单位，维持安慰剂和ecopipam（100 mg p.o.）采用受试者内交叉设计随机排序。在每个8天维持条件的第5天开始，测试考马斯亮蓝自我给药（0、12、25和50 mg）。使用了六次试验选择程序（可卡因与5美元商品代金券），其中包括一次样本试验（参与者吸食当天可用的可卡因剂量）和五次选择试验（参与者在吸食可用的可卡因剂量或接受之间进行选择）。一张商品代金券。结果：在安慰剂可卡因的存在下，ecopipam显着降低可卡因的渴望，同时增加酒精和烟草的渴望。在存在活性可卡因的情况下，ecopipam增加了可卡因自我给药（12 mg），并增加了“良好药物效果”、“高”、“刺激”和剂量质量（25和50 mg）的评级。无论可卡因的剂量如何，Ecopipam都会引起血压的小幅但显著的升高。结论：与安慰剂相比，长效多巴胺D1拮抗剂ecopipam的维持增强了可卡因自我给药及其主观效应。这些数据表明，多巴胺D1受体的慢性拮抗作用可能不是治疗可卡因滥用的有效方法。
Rationale: Data obtained in laboratory animals and humans suggest that dopamine DI receptor antagonists decrease cocaine self-administration and block cocaine's discriminative stimulus and subjective effects. Objectives: This study investigates the effects of the selective dopamine D1 antagonist, ecopipam (SCH 39166), on the reinforcing, cardiovascular, and subjective effects of cocaine in humans. Methods: Ten non-treatment-seeking cocaine smokers (two females, eight males), residing on an inpatient research unit, were maintained on placebo and ecopipam (100 mg p.o.) in random order using a within-subjects, cross-over design. Cocaine self-administration (0, 12, 25, and 50 mg) was tested beginning on the 5th day of each 8-day maintenance condition. A six-trial choice procedure (cocaine vs $5 merchandise vouchers) was utilized, with sessions consisting of one sample trial, when participants smoked the cocaine dose available that day, and five choice trials, when participants chose between smoking the available cocaine dose or receiving one merchandise voucher. Results: In the presence of placebo cocaine, ecopipam significantly decreased cocaine craving while increasing alcohol and tobacco craving. In the presence of active cocaine, ecopipam increased cocaine self-administration (12 mg) and increased ratings of "good drug effect," "high," "stimulated," and dose quality (25 and 50 mg). Ecopipam produced small but significant increases in blood pressure, regardless of cocaine dose. Conclusions: Maintenance on the long-acting dopamine D1 antagonist, ecopipam, enhanced both cocaine self-administration as well as its subjective effects compared to maintenance on placebo. These data suggest that chronic antagonism of the dopamine D1 receptor may not be a useful approach for the treatment of cocaine abuse.