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Alcohol reverses depressive and pronociceptive effects of chronic stress in mice with enhanced activity of the opioid system.

The role of the opioid system in mediating effects of alcoholism and stress in depression is far from clear. We studied, therefore, the effects of chronic mild stress (CMS) and alcohol drinking on depression-like behavior and nociception in lines of mice selected for high (HA) or low (LA) swim stress-induced analgesia. Compared to the LA mice, the HA animals display up-regulation of opioid receptor system function and depression-like behavior in tail suspension test (TST). We report now that alcohol reverses depressive and pronociceptive effect of CMS in HA mice. In contrast, in LA mice CMS does not affect nociception or behavior in TST and the animals are not susceptible to alcohol under CMS. The results suggest that opioid system activity may determine the effects of alcohol on behavior under stress and, therefore, link predispositions to depression and to alcoholism.