Abstinence from chronic cocaine self-administration alters striatal dopamine systems in rhesus monkeys.
Abstinence from chronic cocaine self-administration alters striatal dopamine systems in rhesus monkeys.
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慢性可卡因自我给药的禁欲改变了恒河猴中的纹状体多巴胺系统。
DOI：
10.1038/npp.2008.135
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发表时间：
2009-04
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影响因子：
--
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--
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虽然多巴胺（DA）系统内的失调是慢性可卡因暴露的标志性特征，但这些改变是否持续到戒断的问题在很大程度上仍然没有答案。非人灵长类动物代表了一个理想的模型，以评估长期可卡因暴露后禁欲对DA系统的影响。在这项研究中，雄性恒河猴在固定间隔3分钟的时间表下自我施用可卡因（每次注射0.3 mg/kg，每次30次），持续100天，然后禁欲30天或90天。可卡因自我给药的持续时间以前已被证明可以降低DA D2样受体密度，增加D1样受体和DA转运蛋白（DAT）的水平。在相同的方案和相同的戒断期下，通过提供食物维持对照猴的反应。与对照组动物相比，戒断30天后纹状体所有部分中[3 H]SCH 23390与DA D1受体的结合均显著升高，而[3 H]雷氯必利与DA D2受体的结合在组间无差异。戒断30天后，[3 H]WIN 35 428与DAT的结合在背侧和腹侧纹状体的几乎所有部分也显著更高。然而，90天的禁欲后，DA D1受体和DAT的水平与对照值没有差异。虽然这些结果表明，有最终恢复的DA系统的单独的元素，他们也强调了这些组件的动态性质，在从慢性可卡因自我管理的禁欲的初始阶段。
Although dysregulation within the dopamine (DA) system is a hallmark feature of chronic cocaine exposure, the question of whether these alterations persist into abstinence remains largely unanswered. Nonhuman primates represent an ideal model in which to assess the effects of abstinence on the DA system following chronic cocaine exposure. In this study, male rhesus monkeys self-administered cocaine (0.3 mg/kg per injection, 30 reinforcers per session) under a fixed-interval 3-min schedule for 100 days followed by either 30 or 90 days abstinence. This duration of cocaine self-administration has been previously shown to decrease DA D2-like receptor densities and increase levels of D1-like receptors and DA transporters (DAT). Responding by control monkeys was maintained by food presentation under an identical protocol and the same abstinence periods. [3H]SCH 23390 binding to DA D1 receptors following 30 days of abstinence was significantly higher in all portions of the striatum, compared to control animals, whereas [3H]raclopride binding to DA D2 receptors was not different between groups. [3H]WIN 35 428 binding to DAT was also significantly higher throughout virtually all portions of the dorsal and ventral striatum following 30 days of abstinence. Following 90 days of abstinence, however, levels of DA D1 receptors and DAT were not different from control values. Although these results indicate that there is eventual recovery of the separate elements of the DA system, they also highlight the dynamic nature of these components during the initial phases of abstinence from chronic cocaine self-administration.
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