Opioid system /EtOH abuse: molecular genetic manipulat.

阿片受体在乙醇依赖中的作用的分子遗传学研究方法最近取得了令人着迷的结果。敲除μ阿片受体的非依赖性小鼠阻断了乙醇饮用和对乙醇的操作性反应。相反，δ受体的敲除产生乙醇偏好和乙醇的操作性响应的时间依赖性增加，其与敲除动物的焦虑样响应相关。这些研究的局限性在于：（i）这些研究基于阿片受体基因的组成性操纵，因此在发育过程中可能发生代偿机制，并解释了观察到的表型;（ii）阿片受体的敲除发生在整个大脑和身体。为了解决这些问题，新的分子遗传学方法将用于产生μ和δ受体的条件性敲除。将尝试在成人中敲除这些受体，并且在与INIA关于扩展杏仁核在过量饮酒中的假设作用的总体假设一致的特定脑区域中敲除这些受体。

The molecular genetic approach to the study of the role of opioid receptors in ethanol dependence has recently yielded fascinating results. The non-dependent mice, knockout of the mu opioid receptor blocks ethanol drinking and operant responding for ethanol. In contrast, knockout of the delta receptor produces a time-dependent increase in ethanol preference and operant responding for ethanol that correlates with anxiety-like responses of the knockout animals. The limitations of these studies are that (i) these studies are based on constitutive manipulation of opioid receptor genes, therefore compensatory mechanisms could take place during development and account for the observed phenotypes and (ii) the knockout of the opioid receptors occurs throughout the brain and body. To address these issues, novel molecular genetic approaches will be used to produce conditional knockouts of mu and delta receptors. An attempt will be made to knockout these receptors in the adult, and in specific brain regions consistent with the overall hypothesis of INIA regarding the hypothesized role of the extended amygdala in excessive alcohol consumption.