Alcohol use disorder is highly comorbid with other neuropsychiatric disorders such as depression and anxiety. Importantly, women and men are affected differentially by heavy drinking, with women experiencing longer negative affective states after intoxication and increased likelihood to present with comorbid mood or anxiety disorders. In rodents, several studies using different alcohol administration models have shown the development of depressive-like or anxiety-like phenotypes that emerge during abstinence. In this study, we compared the emergence of negative affective behaviors during abstinence from 7 weeks of two-bottle choice intermittent access to 20% alcohol in male and female C57BL/6J mice, a drinking paradigm little studied in this context. Half of the mice were tested 24 hours into abstinence on the elevated zero maze and 19–20 days into abstinence in a novel object in the home cage encounter test. The other half of the mice were tested 27–28 days into abstinence with the novelty-suppressed feeding test. As expected, females drank more than males across the 7 weeks of access to alcohol. Drinking history did not affect performance on these tasks, with the exception of increasing the number of open arm entries on the elevated zero maze. Interestingly, in alcohol-naïve mice, females showed fewer anxiety-like behaviors than males in the elevated zero maze and the novelty-suppressed feeding test. Our results suggest that the intermittent access model does not reliably induce negative affective behaviors on these tasks, and that behavior in female and male mice differs across these tests. Rather, intermittent alcohol drinking may induce a mild form of behavioral disinhibition. Thus, the model of alcohol access is a critical factor in determining the appearance of behavioral disturbances that emerge during abstinence.

酒精使用障碍与其他神经精神障碍如抑郁和焦虑高度共存。重要的是，女性和男性受到大量饮酒的影响不同，女性在醉酒后经历更长的负面情感状态，并且出现共病情绪或焦虑症的可能性增加。在啮齿类动物中，使用不同酒精给药模型的几项研究表明，在戒酒期间会出现抑郁样或焦虑样表型。在这项研究中，我们比较了雄性和雌性 C57BL/6J 小鼠从 7 周两瓶选择间歇性获得 20% 酒精的禁欲期间出现的负面情感行为，这种饮酒范式在这方面的研究很少。一半的老鼠在高架零迷宫中禁欲 24 小时，在家庭笼子遭遇测试中禁欲 19-20 天。另一半小鼠在禁欲 27-28 天后接受新奇抑制喂养试验。正如预期的那样，在接触酒精的 7 周内，女性比男性喝得更多。饮酒史不会影响这些任务的表现，除了在高架零迷宫上增加开放臂条目的数量。有趣的是，在从未接触过酒精的小鼠中，在高架零迷宫和新奇抑制喂养测试中，雌性比雄性表现出更少的焦虑样行为。我们的结果表明，间歇性访问模型不能可靠地诱导这些任务的负面情感行为，并且雌性和雄性小鼠的行为在这些测试中有所不同。相反，间歇性饮酒可能会导致轻微的行为去抑制。因此，酒精获取模型是确定戒酒期间出现的行为障碍的关键因素。