Binge drinking is a widespread public health concern with limited effective treatment options. To better select pharmaceutical targets, it is imperative to expand our knowledge of the underlying neural mechanisms involved in binge drinking. Our previous experiments in C57BL/6J female mice found that increasing activity in the nucleus accumbens (NAc) core using excitatory Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) reduced binge-like drinking. These results differed from what has been found in males; however, it is unclear whether differences in experimental procedures or sex underlie these discrepancies. We matched the conditions used in our female study and asked whether bidirectional manipulation of NAc core activity has different effects on binge-like drinking in males. Male C57BL/6J mice were stereotaxically injected with AAV2 hSyn-HA hM3Dq (excitatory), -hM4Di (inhibitory), or -eGFP bilaterally into the NAc core. We tested the effects of altering NAc activity on binge-like ethanol intake using Drinking in the Dark (DID). During the first week, mice were pre-treated with vehicle to establish baseline ethanol intake. In week 2, mice were treated with 1 mg/kg CNO prior to DID to determine the effects of DREADD-induced changes in NAc core activity on ethanol intake. Decreasing activity via CNO/hM4Di significantly decreased binge-like drinking in male mice relative to eGFP and hM4Di groups. We also measured intake of sucrose, quinine, and water after CNO treatment and found that increasing NAc core activity via CNO/hM3Dq increased quinine intake, and increased water intake over time. We did not observe significant differences in the GFP or hM4Di groups. This work suggests there exist apparent sex-related differences in NAc core contributions to binge-like alcohol drinking, thus demonstrating the need for inclusion of both sexes in future work.

酗酒是一个广泛的公共卫生问题，有效的治疗选择有限。为了更好地选择药物靶点，必须扩大我们对酗酒所涉及的潜在神经机制的了解。我们之前在 C57BL/6J 雌性小鼠中进行的实验发现，使用设计药物独家激活的兴奋性设计受体 (DREADD) 增加伏隔核 (NAc) 核心的活性可减少暴饮暴食。这些结果与在男性中发现的结果不同。然而，目前尚不清楚这些差异是否是实验程序或性别的差异造成的。我们匹配了女性研究中使用的条件，并询问 NAc 核心活性的双向操纵是否对男性的暴饮暴食有不同的影响。将AAV2 hSyn-HA hM3Dq（兴奋性）、-hM4Di（抑制性）或-eGFP双侧立体定位注射到雄性C57BL/6J小鼠NAc核心中。我们使用黑暗中饮酒 (DID) 测试了改变 NAc 活性对暴饮暴食乙醇摄入量的影响。在第一周，用媒介物对小鼠进行预处理以确定乙醇摄入量的基线。第 2 周，在 DID 之前用 1 mg/kg CNO 处理小鼠，以确定 DREADD 诱导的 NAc 核心活性变化对乙醇摄入的影响。相对于 eGFP 和 hM4Di 组，通过 CNO/hM4Di 降低活性可显着减少雄性小鼠的暴饮行为。我们还测量了 CNO 处理后蔗糖、奎宁和水的摄入量，发现通过 CNO/hM3Dq 增加 NAc 核心活性会增加奎宁摄入量，并随着时间的推移增加水摄入量。我们没有观察到 GFP 或 hM4Di 组有显着差异。 这项工作表明，NAc 对酗酒的核心贡献存在明显的性别相关差异，从而表明在未来的工作中需要将两种性别都纳入其中。