Aripiprazole attenuates the discriminative-stimulus and subject-rated effects of D-amphetamine in humans
Aripiprazole attenuates the discriminative-stimulus and subject-rated effects of D-amphetamine in humans
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DOI：
10.1038/sj.npp.1300803
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发表时间：
2005-11-01
影响因子：
7.6
通讯作者：
Rush, CR
中科院分区：
文献类型：
--
作者：
Lile, JA;Stoops, WW;Rush, CR
动物研究结果表明，使用多巴胺 (DA) D-2 受体部分激动剂可能是治疗兴奋剂依赖的有效策略。阿立哌唑是一种非典型抗精神病药，对 D2 受体具有部分激动剂活性。在这项实验中，七名有非治疗性兴奋剂使用史的人类参与者学会了辨别 15 毫克口服 D-安非他明。在获得辨别力(即连续四次会话中>=80%正确响应)后，评估一系列剂量的D-苯丙胺(0、2.5、5、10和15mg)单独和与阿立哌唑(0和20mg)组合的效果。单独的D-安非他明起到辨别刺激的作用，产生典型的受试者评级药物效应（例如活跃、警觉、精力充沛的评级增加）和心血管指数升高。这些效应通常是剂量的函数。单独使用阿立哌唑不会引起 D-苯丙胺适当的反应或产生受试者评价的效果，但会适度损害表现。阿立哌唑的施用显着减弱了 D-安非他明的辨别刺激和心血管作用，以及一些受试者评价的药物作用。这些数据与之前的临床前研究结果一致，表明 DA 部分激动剂作为治疗兴奋剂依赖的潜在药物疗法值得进一步评估。未来的研究应该调查阿立哌唑或相关化合物是否能够减弱与较高程度的依赖相关的兴奋剂（例如甲基苯丙胺或可卡因）对依赖个体的行为影响。
The results of animal research suggest that the use of partial agonists at dopamine (DA) D-2 receptors may be an effective strategy for the treatment of stimulant dependence. Aripiprazole is an atypical antipsychotic that has partial agonist activity at D2 receptors. In this experiment, seven human participants with a history of nontherapeutic stimulant use learned to discriminate 15 mg oral D-amphetamine. After acquiring the discrimination (ie >= 80% correct responding on four consecutive sessions), the effects of a range of doses Of D-amphetamine (0, 2.5, 5, 10, and 15 mg), alone and in combination with aripiprazole (0 and 20 mg), were assessed. D-Amphetamine alone functioned as a discriminative stimulus, produced prototypical subject-rated drug effects (eg increased ratings of Active, Alert, Energetic) and elevated cardiovascular indices, These effects were generally a function of dose. Aripiprazole alone did not occasion D-amphetamine-appropriate responding or produce subject-rated effects, but modestly impaired performance. Administration of aripiprazole significantly attenuated the discriminative-stimulus and cardiovascular effects Of D-amphetamine, as well as some of the subject-rated drug effects. These data are consistent with previous preclinical findings and suggest that DA partial agonists deserve further evaluation as potential pharmacotherapies in the management of stimulant dependence. Future studies should investigate the ability of aripiprazole or related compounds to attenuate the behavioral effects of stimulants associated with a greater degree of dependence, such as methamphetamine or cocaine, in dependent individuals.