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阿立哌唑在复发动物模型中可阻断对可卡因觅求行为的恢复。

Aripiprazole blocks reinstatement of cocaine seeking in an animal model of relapse.

作者信息

Feltenstein Matthew W, Altar C Anthony, See Ronald E

机构信息

Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina 29425, USA.

出版信息

Biol Psychiatry. 2007 Mar 1;61(5):582-90. doi: 10.1016/j.biopsych.2006.04.010. Epub 2006 Jun 27.

Abstract

BACKGROUND

Aripiprazole (Abilify) is an atypical antipsychotic drug primarily characterized by partial agonist activity at dopamine (DA) D2 receptors and low side effects. Based on pharmacologic properties that include a stabilization of mesocorticolimbic DA activity, a pathway implicated in addiction, aripiprazole was tested for its ability to prevent relapse to cocaine seeking in rats.

METHODS

We assessed the dose-dependent effects of aripiprazole on conditioned cue-induced and cocaine-primed reinstatement of drug-seeking behavior following chronic intravenous cocaine self-administration in an animal model of relapse.

RESULTS

Aripiprazole potently and dose-dependently attenuated responding on the previously cocaine-paired lever during both reinstatement conditions, with slightly greater efficacy at reducing conditioned-cued reinstatement. Aripiprazole was effective at doses that failed to alter cocaine self-administration, food self-administration, reinstatement of food-seeking behavior, or basal locomotor activity, suggesting selective effects of aripiprazole on motivated drug-seeking behavior.

CONCLUSIONS

These results in a relapse model show that aripiprazole can block cocaine seeking without affecting other behaviors. The D2 partial agonist properties of aripiprazole likely account for the blockade of reinstatement of cocaine-seeking behavior. Given its established efficacy and tolerability as a treatment for psychosis, aripiprazole may be an excellent therapeutic choice for reducing craving and preventing relapse in people with cocaine dependency.

摘要

背景

阿立哌唑(安律凡)是一种非典型抗精神病药物,主要特点是对多巴胺(DA)D2受体具有部分激动剂活性且副作用低。基于包括稳定中脑边缘多巴胺活性(一条与成瘾有关的途径)在内的药理特性,对阿立哌唑预防大鼠可卡因觅求复发的能力进行了测试。

方法

在复发动物模型中,我们评估了阿立哌唑对慢性静脉注射可卡因自我给药后条件性线索诱导和可卡因激发的觅药行为恢复的剂量依赖性影响。

结果

在两种恢复条件下,阿立哌唑均能有效且剂量依赖性地减弱先前与可卡因配对杠杆上的反应,在减少条件性线索诱导的恢复方面效果稍好。阿立哌唑在不改变可卡因自我给药、食物自我给药、食物觅求行为恢复或基础运动活动的剂量下有效,表明阿立哌唑对动机性觅药行为具有选择性作用。

结论

在复发模型中的这些结果表明,阿立哌唑可以阻断可卡因觅求而不影响其他行为。阿立哌唑的D2部分激动剂特性可能是其阻断可卡因觅求行为恢复的原因。鉴于其作为精神病治疗药物已确立的疗效和耐受性,阿立哌唑可能是减少可卡因依赖者的渴望和预防复发的极佳治疗选择。

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