Investigating Methamphetamine Craving Using the Extinction-Reinstatement Model in the Rat.

Peter R Kufahl, M Foster Olive
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Abstract

Like all other drugs of abuse, the primary therapeutic objective for treating methamphetamine addiction research is the maintenance of abstinence and prevention of relapse to habitual drug-taking. Compounds with the potential to prevent relapse are often investigated in rats that are trained to self-administer intravenous methamphetamine, subjected to extinction training where responding is no longer reinforced, and then given tests for reinstatement of drug-seeking behavior triggered by methamphetamine injections or re-exposure to drug-paired cues. Experimental compounds are administered to the animals prior to the reinstatement tests to evaluate their potential for attenuating or preventing drug-seeking behavior. This article describes the common procedures of the extinction-reinstatement model in studies of this type, and identifies areas of discrepancy. This is followed by a comprehensive overview of the currently published anti-reinstatement effects of pharmacological compounds, classified by the most relevant neurological systems associated with these compounds. The article concludes with a brief discussion of how the study of anti-reinstatement effects can be expanded to further verify existing positive results or to find novel neurobiological targets.

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利用消退-再刺激模型研究大鼠对甲基苯丙胺的渴求。
与所有其他滥用药物一样,治疗甲基苯丙胺成瘾研究的主要治疗目标是维持戒断和防止习惯性吸毒复发。具有预防复吸潜力的化合物通常在大鼠身上进行研究,训练大鼠自我静脉注射甲基苯丙胺,对大鼠进行消退训练,不再强化大鼠的反应,然后对注射甲基苯丙胺或再次接触毒品配对线索引发的觅毒行为进行恢复测试。在进行恢复测试之前,会给动物注射实验化合物,以评估其减弱或预防觅药行为的潜力。本文介绍了此类研究中消退-恢复模型的常用程序,并指出了存在差异的地方。随后,文章按照与这些化合物最相关的神经系统分类,全面概述了目前已发表的药理化合物的抗恢复效果。文章最后简要讨论了如何扩展抗恢复效应的研究,以进一步验证现有的积极结果或寻找新的神经生物学靶点。
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