反复饮酒会导致许多神经精神疾病,包括酒精使用障碍和共同表达的焦虑和情绪障碍。具有与男性相同的酒精暴露史的女性更容易患这些疾病的发展和表达,这表明他们可能对控制饮酒的边缘大脑区域的酒精诱导的可塑性更敏感,应激反应性,和奖励处理,在其他行为中。使用恒河猴饮酒的翻译模型,我们检查了终末纹(BNST)床核神经元的基础功能和可塑性的性别差异,在患有焦虑和酒精使用障碍的人中,杏仁核中的一个大脑区域显示为中枢回路节点失调。在每天“开放获取”(22小时/天)到4%乙醇和水超过一年或对照条件后,我们对雄性和雌性猴子的BNST神经元进行了切片电生理记录。我们发现来自对照雌性的BNST神经元的总电流密度降低,超极化激活去极化电流(Ih),和内部整顿,以及更高的膜阻力和更大的突触谷氨酸能释放和兴奋性驱动,比那些来自控制男性的人,表明女性BNST神经元比男性神经元更基本兴奋。长期饮酒导致男女两性的这些措施发生了变化,降低电流密度,Ih,向内整流和增加突触兴奋。此外,网络活动依赖性突触抑制在男性的BNST神经元中基本高于女性,酒精暴露增加了两性的这种情况,对抗过度兴奋的推定体内平衡机制。总之,这些结果表明,恒河猴BNST在女性中的基础兴奋程度高于男性,长期饮酒会导致兴奋性和突触兴奋的整体增加。这些结果揭示了导致女性对神经精神疾病的易感性的机制,包括共同表达的焦虑和酒精使用障碍。
Repeated alcohol drinking contributes to a number of neuropsychiatric diseases, including alcohol use disorder and co-expressed anxiety and mood disorders. Women are more susceptible to the development and expression of these diseases with the same history of alcohol exposure as men, suggesting they may be more sensitive to alcohol-induced plasticity in limbic brain regions controlling alcohol drinking, stress responsivity, and reward processing, among other behaviors. Using a translational model of alcohol drinking in rhesus monkeys, we examined sex differences in the basal function and plasticity of neurons in the bed nucleus of the stria terminalis (BNST), a brain region in the extended amygdala shown to be a hub circuit node dysregulated in individuals with anxiety and alcohol use disorder. We performed slice electrophysiology recordings from BNST neurons in male and female monkeys following daily \"open access\" (22 h/day) to 4% ethanol and water for more than one year or control conditions. We found that BNST neurons from control females had reduced overall current density, hyperpolarization-activated depolarizing current (Ih), and inward rectification, as well as higher membrane resistance and greater synaptic glutamatergic release and excitatory drive, than those from control males, suggesting that female BNST neurons are more basally excited than those from males. Chronic alcohol drinking produced a shift in these measures in both sexes, decreasing current density, Ih, and inward rectification and increasing synaptic excitation. In addition, network activity-dependent synaptic inhibition was basally higher in BNST neurons of males than females, and alcohol exposure increased this in both sexes, a putative homeostatic mechanism to counter hyperexcitability. Altogether, these results suggest that the rhesus BNST is more basally excited in females than males and chronic alcohol drinking produces an overall increase in excitability and synaptic excitation. These results shed light on the mechanisms contributing to the female-biased susceptibility to neuropsychiatric diseases including co-expressed anxiety and alcohol use disorder.