Excessive, binge drinking is a major contributor to the great harm and cost of alcohol use disorder. We recently showed, using both limited and intermittent-access two-bottle-choice models, that inhibiting nucleus accumbens shell (Shell) orexin-1-receptors (Ox1Rs) reduces alcohol intake in higher-drinking male C57BL/6 mice (Lei et al., 2019). Other studies implicate Ox1Rs, tested systemically, for several higher-drinking models, including the single-bottle, Rhodes Drinking-in-the-Dark paradigm. Here, we report studies examining whether Shell Ox1Rs contribute to alcohol intake in male mice using a single-bottle Limited Daily Access (LDA) drinking model modified from drinking-in-the-dark paradigms (2-h access starting 3 h into the dark cycle, 5 days per week). In addition, some previous work has suggested possible differences in circuitry for one- versus two-choice behaviors, and thus other mice first drank under a single-bottle schedule, and then an additional water bottle was included 2 days a week starting in week 3. Surprisingly, at the same time we were determining Ox1R importance for two-bottle-choice models, parallel studies found that inhibiting Shell Ox1Rs had no impact on drinking using the single-bottle LDA model, or when a second bottle containing water was added later during drinking. Furthermore, we have related Shell Ox1R regulation of intake to basal consumption, but no such pattern was observed with single-bottle LDA drinking. Thus, unlike our previous work showing the importance of Shell Ox1Rs for male alcohol drinking under several two-bottle-choice models, Shell Ox1Rs were not required under a single-bottle paradigm, even if a second water-containing bottle was later added. These results raise the speculations that different mechanisms could promote intake under single- versus two-bottle access conditions, and that the conditions under which an animal learns to drink can impact circuitry driving future intake.

过度酗酒是导致酒精使用障碍的巨大危害和代价的主要因素。我们最近使用有​​限的和间歇性的两瓶选择模型表明，抑制伏隔核壳 (Shell) 食欲素 1 受体 (Ox1Rs) 可减少饮酒量较高的雄性 C57BL/6 小鼠的酒精摄入量（Lei 等人., 2019)。其他研究涉及 Ox1Rs，系统测试，用于几种高饮酒模型，包括单瓶，罗德在黑暗中饮酒范式。在这里，我们报告了使用从黑暗中饮酒范式（2 小时进入黑暗中 3 小时开始）修改的单瓶有限每日访问 (LDA) 饮酒模型检查壳牌 Ox1Rs 是否有助于雄性小鼠酒精摄入的研究周期，每周 5 天）。此外，之前的一些研究表明，单选择和双选择行为的电路可能存在差异，因此其他小鼠首先按照单瓶计划喝水，然后从第 3 周开始每周 2 天额外加入一瓶水。 令人惊讶的是，在我们确定 Ox1R 对双瓶选择模型的重要性的同时，平行研究发现抑制 Shell Ox1Rs 对使用单瓶 LDA 模型的饮酒没有影响，或者在饮用过程中稍后添加第二瓶装水时。此外，我们将 Shell Ox1R 的摄入量调节与基础消耗量相关联，但在单瓶 LDA 饮用中未观察到这种模式。因此，与我们之前的工作不同，我们在几个两瓶选择模型下展示了 Shell Ox1Rs 对男性饮酒的重要性，在单瓶模式下不需要壳牌 Ox1R，即使后来添加了第二个装水瓶。这些结果引发了一种推测，即在单瓶和两瓶访问条件下不同的机制可以促进摄入，并且动物学习饮酒的条件会影响驱动未来摄入的电路。