Opioid system /EtOH abuse: molecular genetic manipulat.

研究阿片受体在酒精依赖中的作用的分子遗传学方法最近取得了令人着迷的结果。非依赖的小鼠，Mu阿片受体的敲除阻止了酒精的饮用和对酒精的有效反应。相比之下，Delta受体的敲除会产生与时间相关的乙醇偏好和对乙醇的操作型反应，这与基因敲除动物的焦虑样反应相关。这些研究的局限性是：(I)这些研究基于阿片受体基因的结构性操作，因此代偿机制可能发生在发育过程中，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，将使用新的分子遗传学方法来产生有条件的Mu和Delta受体敲除。将尝试敲除成人的这些受体，并在特定的大脑区域中敲除这些受体，这与INIA关于杏仁核在过量饮酒中的假设作用的总体假说一致。

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.