Department of Biology, Penn State University, United States of America.
Department of Biology, Penn State University, United States of America; Neuroscience Curriculum, HUCK Institute of the Life Sciences, Penn State University, United States of America.
Brain Res Bull. 2022 Aug;186:38-46. doi: 10.1016/j.brainresbull.2022.05.010. Epub 2022 May 25.
Alcohol use disorder (AUD) is characterized by alcohol use coupled with chronic relapse and involves brain regions including the bed nucleus of the stria terminalis (BNST). Here, we explore whether a subpopulation of BNST neurons, somatostatin (SST) expressing GABAergic neurons, play a role in an animal model of binge-like alcohol consumption, the Drinking in the Dark (DID) model. Chemogenetic activation of BNST SST neurons reduced binge alcohol consumption in female but not male SST-Cre mice, while inhibition of these neurons in the same mice had no effect. In addition, chemogenetic activation of these neurons did not cause apparent changes in models of anxiety-like behavior in either sex. Basal SST cell counts and intrinsic excitability of SST neurons were compared to attempt to understand sex differences in DREADD-induced changes in drinking, and while males had a greater number of BNST SST neurons, this effect went away when normalizing for total BNST volume. Together, these results suggest SST neurons in the BNST should be further explored as a potential neuronal subtype modulated by AUD, and for their therapeutic potential.
酒精使用障碍(AUD)的特征是饮酒伴随着慢性复发,涉及包括终纹床核(BNST)在内的大脑区域。在这里,我们探讨了 BNST 中的一个亚群神经元,即生长抑素(SST)表达 GABA 能神经元,是否在 binge-like 酒精消费的动物模型(即暗饮模型)中发挥作用。BNST SST 神经元的化学遗传激活减少了雌性而非雄性 SST-Cre 小鼠的 binge 酒精消费,而在相同小鼠中抑制这些神经元则没有效果。此外,在这两种性别中,化学遗传激活这些神经元对焦虑样行为模型均未引起明显变化。比较了基础 SST 细胞计数和 SST 神经元的内在兴奋性,以试图了解 DREADD 诱导的饮酒变化中的性别差异,尽管雄性 BNST SST 神经元数量较多,但当对 BNST 总容积进行归一化时,这种影响就消失了。综上所述,这些结果表明 BNST 中的 SST 神经元应该作为 AUD 调节的潜在神经元亚型进一步研究,以探索其治疗潜力。