Opioid system /EtOH abuse: molecular genetic manipulat.

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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.