Haun Harold L, D'Ambrosio Shannon L, Pati Dipanwita, Taxier Lisa R, Kash Thomas L
Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599, USA.
Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, 27599, USA.
Addict Neurosci. 2022 Sep;3. doi: 10.1016/j.addicn.2022.100023. Epub 2022 Jun 15.
Binge drinking is a common pattern of excessive alcohol consumption associated with Alcohol Use Disorder (AUD) and unraveling the neurocircuitry that promotes this type of drinking is critical to the development of novel therapeutic interventions. The septal region was once a focal point of alcohol research yet has seen limited study over the last decade in relation to binge drinking. Numerous studies point to involvement of the dorsal septum (dSep) in excessive drinking and withdrawal, but few studies have manipulated this region in the context of binge drinking behavior. The present experiments were primarily designed to determine the effect of chemogenetic manipulation of the dSep on binge-like alcohol drinking in male and female C57BL/6J mice. Mice received bilateral infusion of AAVs harboring hM4Di, hM3Dq, or mCherry into the dSep and subjects were challenged with systemic administration of clozapine--oxide (CNO) and vehicle in the context of binge-like alcohol consumption, locomotor activity, and sucrose drinking. CNO-mediated activation (hM3Dq) of the dSep resulted in increased binge-like alcohol consumption, locomotor activity, and sucrose intake in males. DSep activation promoted sucrose drinking in female mice, but alcohol intake and locomotor activity were unaffected. Conversely, silencing (hM4Di) of the dSep modestly decreased locomotor activity in males and did not influence alcohol or sucrose intake in either sex. These data support a role for the dSep in promoting binge-like drinking behavior in a sex-dependent fashion and suggests a broad role for the region in the modulation of general appetitive behaviors and locomotor activity.
暴饮是一种与酒精使用障碍（AUD）相关的常见过度饮酒模式，阐明促进这种饮酒类型的神经回路对于开发新的治疗干预措施至关重要。隔区曾经是酒精研究的焦点，但在过去十年中，与暴饮相关的研究有限。大量研究表明背侧隔区（dSep）参与过度饮酒和戒断，但很少有研究在暴饮行为的背景下对该区域进行操控。本实验主要旨在确定对雄性和雌性C57BL/6J小鼠的dSep进行化学遗传操控对类似暴饮的酒精饮用的影响。小鼠双侧接受向dSep注射携带hM4Di、hM3Dq或mCherry的腺相关病毒（AAV），并在类似暴饮的酒精消费、运动活动和蔗糖饮用的背景下，用氯氮平氧化物（CNO）和赋形剂进行全身给药挑战。CNO介导的dSep激活（hM3Dq）导致雄性小鼠类似暴饮的酒精消费、运动活动和蔗糖摄入量增加。dSep激活促进了雌性小鼠的蔗糖饮用，但酒精摄入量和运动活动未受影响。相反，dSep的沉默（hM4Di）适度降低了雄性小鼠的运动活动，并且对两性的酒精或蔗糖摄入量均无影响。这些数据支持dSep在以性别依赖的方式促进类似暴饮的饮酒行为中发挥作用，并表明该区域在调节一般食欲行为和运动活动中具有广泛作用。
