Opioid system /EtOH abuse: molecular genetic manipulat.

分子遗传学方法研究阿片受体在乙醇依赖中的作用最近取得了令人着迷的结果。非依赖性小鼠，敲除mu阿片受体阻断乙醇饮用和对乙醇的操作反应。相反，敲除δ受体会产生乙醇偏好和乙醇操作性反应的时间依赖性增加，这与敲除动物的焦虑样反应相关。这些研究的局限性在于：(i)这些研究是基于对阿片受体基因的构成性操纵，因此代偿机制可能在发育过程中发生，并解释观察到的表型；（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mu和delta受体的条件敲除。我们将尝试在成人和特定大脑区域敲除这些受体，这些区域与INIA的总体假设一致，即延长的杏仁核在过度饮酒中的假设作用。

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.