Molecular Mechanisms Underlying Opiate Addiction: Implications for Medications Development

Eric J. Nestler
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引用次数: 19

Abstract

Progress is being made in identifying molecular and cellular adaptations induced in specific brain regions by long-term opiate exposure and in relating these adaptations to specific aspects of opiate addiction. In the locus coeruleus, the major noradrenergic nucleus in brain which plays an important role in physical opiate dependence and withdrawal, upregulation of the cAMP pathway in response to chronic opiate administration has been shown to be one important mechanism involved. In the mesolimbic dopamine system, which plays an important role in the reinforcing effects of opiates after short- and long-term exposure, some similar and some different types of opiate-induced adaptations have been identified. As an increasingly complete understanding of opiate action is obtained, this knowledge will provide the framework for the development of novel therapeutic agents to treat opiate addiction.

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阿片成瘾的分子机制:对药物开发的启示
在确定长期阿片类药物暴露在特定脑区诱导的分子和细胞适应以及将这些适应与阿片类药物成瘾的特定方面联系起来方面正在取得进展。蓝斑核是大脑中主要的去肾上腺素能核,在阿片类药物的物理依赖和戒断中起重要作用,cAMP通路在慢性阿片类药物给药反应中的上调已被证明是其中一个重要机制。中边缘多巴胺系统在阿片类药物短期和长期暴露后的强化效应中起重要作用,在该系统中发现了一些相似和不同类型的阿片类药物诱导适应。随着对阿片类药物作用越来越全面的了解,这一知识将为开发治疗阿片类药物成瘾的新型治疗药物提供框架。
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