PDF(Pubmed)
Abstract：
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-N-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.
摘要：
暴饮暴食是与酒精使用障碍（AUD）相关的过度饮酒的常见模式，解开促进这种饮酒的神经回路对于开发新的治疗干预措施至关重要。间隔区域曾经是酒精研究的重点，但在过去十年中，与暴饮暴食有关的研究有限。许多研究指出，背隔（dSep）参与过度饮酒和戒断，但是很少有研究在暴饮暴食行为的背景下操纵这个地区。本实验主要设计用于确定dSep的化学遗传学操作对雄性和雌性C57BL/6J小鼠暴饮暴食样饮酒的影响。小鼠接受双侧输注携带hM4Di的AAV，hM3Dq,或mCherry进入dSep，在暴饮暴食的情况下，受试者被全身施用氯氮平-N-氧化物（CNO）和载体的挑战，运动活动，和蔗糖饮用。CNO介导的dSep激活（hM3Dq）导致暴饮暴食样饮酒增加，运动活动，和男性的蔗糖摄入量。DSep激活促进雌性小鼠的蔗糖饮用，但酒精摄入量和运动活动不受影响。相反，dSep的沉默（hM4Di）适度降低了男性的运动活动，并且不影响两种性别的酒精或蔗糖摄入量。这些数据支持dSep在以性别依赖性方式促进暴饮暴食行为方面的作用，并表明该地区在调节一般食欲行为和运动活动方面的广泛作用。
