Department of Neurology, University of California at San Francisco, San Francisco, CA, United States.
Department of Neurology, University of California at San Francisco, San Francisco, CA, United States; Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, United States.
Alcohol. 2020 Dec;89:139-146. doi: 10.1016/j.alcohol.2020.09.003. Epub 2020 Sep 25.
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.
过量饮酒和狂饮是导致酒精使用障碍造成巨大危害和代价的主要因素。我们最近使用有限和间歇性双瓶选择模型表明，抑制伏隔核壳（Shell）食欲素-1-受体（Ox1Rs）可减少更高饮酒量的雄性 C57BL/6 小鼠的酒精摄入量（Lei 等人，2019 年）。其他研究表明，系统测试的 Ox1Rs 与几种更高饮酒量模型有关，包括单瓶 Rhodes 暗时饮酒模型。在这里，我们报告了使用单瓶限时每日访问（LDA）饮酒模型的研究，该模型是从暗时饮酒模型修改而来的，以检查壳层 Ox1Rs 是否有助于雄性小鼠的酒精摄入量（黑暗周期 3 小时开始时的 2 小时访问，每周 5 天）。此外，以前的一些工作表明，对于单瓶和双瓶选择行为，电路可能存在差异，因此，一些老鼠首先在单瓶计划下饮酒，然后从第 3 周开始每周 2 天增加一瓶水。令人惊讶的是，当我们确定 Ox1R 对双瓶选择模型的重要性时，平行研究发现，抑制壳层 Ox1Rs 对单瓶 LDA 模型的饮酒没有影响，或者当稍后在饮酒过程中添加含有水的第二瓶时也没有影响。此外，我们已经将壳层 Ox1R 对摄入量的调节与基础消耗量相关联，但在单瓶 LDA 饮酒中没有观察到这种模式。因此，与我们之前的工作不同，该工作表明在几种双瓶选择模型下，壳层 Ox1Rs 对雄性酒精饮酒的重要性，壳层 Ox1Rs 在单瓶范式下不需要，即使稍后添加了第二瓶含水瓶。这些结果提出了一些推测，即不同的机制可能会在单瓶和双瓶摄入条件下促进摄入，并且动物学习饮酒的条件可能会影响未来摄入的驱动电路。
