Sex differences in the synergistic effect of prior binge drinking and traumatic stress on subsequent ethanol intake and neurochemical responses in adult C57BL/6J mice
Sex differences in the synergistic effect of prior binge drinking and traumatic stress on subsequent ethanol intake and neurochemical responses in adult C57BL/6J mice
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DOI：
10.1016/j.alcohol.2018.02.004
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发表时间：
2018-09-01
期刊：
影响因子：
2.3
通讯作者：
Devaud, Leslie L.
中科院分区：
文献类型：
--
作者：
Finn, Deborah A.;Helms, Melinda L.;Devaud, Leslie L.
酒精使用障碍（AUD）的特征是反复发作的酗酒。基于报告，暴露于捕食者气味应激（PS）一贯增加乙醇摄入量，本研究探讨是否以前的酗酒差异改变响应PS和随后的乙醇摄入量在雄性和雌性小鼠相比，小鼠没有以前的酗酒暴露。在未处理过的雄性和雌性C57 BL/6 J小鼠中进行的初步研究证实，暴露于脏大鼠垫料30分钟显著增加血浆皮质酮（CORT）水平和焦虑相关行为，证明在随后的饮酒研究中使用脏大鼠垫料作为PS是合理的。接下来，不同的雄性和雌性C57 BL/6 J小鼠组接受了7次酒精狂欢（狂欢）或喝水（对照），随后是1个月的禁欲期。然后，2瓶选择乙醇摄入量（10%或10 E相对于水，23小时/天）在Lickometer室中测量4周。基线摄入量稳定后，与基线和对照组相比，暴露于间歇性PS（2x /周x 2周）显著增加了雄性（而非雌性）狂欢小鼠第2次PS后的乙醇摄入量。然而，在一个雌性亚组（基线较低）中，与基线相比，PS在对照组和狂欢组小鼠中产生了相似的10 E摄入量增加。舔行为的分析确定，在狂欢雄性小鼠和雌性低基线亚组中，10 E摄入量的增加与10 E回合频率和10 E舔在整个昼夜节律黑暗阶段的显著增加相关。因此，PS显着增加10 E摄入量，并有协同作用与先前的酗酒男性，而PS产生了类似的显着增加10 E摄入量的低基线亚组的狂欢和对照组女性。血浆CORT水平显着增加狂欢和对照组动物后PS。从每日10 E摄入量中撤出24小时的CORT水平在10 E舔量升高的组中最高（即，暴食雄性和对照雌性）。在24小时戒断时，雄性和雌性小鼠的前额叶皮层（PFC）和海马（HC）中GABA（A）受体α 1亚单位、促肾上腺皮质激素释放因子受体1和糖皮质激素受体的蛋白水平与年龄匹配的不同组的幼稚小鼠的水平相比发生了差异性改变，HC的变化大于PFC，雌性的变化大于雄性。重要的是，PFC和HC中蛋白质水平的性别差异性变化增加了受压力和酗酒影响的神经化学系统的性别差异的证据，并为治疗AUG的性别特异性药理学策略提供了论据。爱思唯尔公司出版
Alcohol-use disorders (AUDs) are characterized by repeated episodes of binge drinking. Based on reports that exposure to predator odor stress (PS) consistently increases ethanol intake, the present studies examined whether prior binge drinking differentially altered responsivity to PS and subsequent ethanol intake in male and female mice, when compared to mice without prior binge exposure. Initial studies in na ve male and female C57BL/6J mice confirmed that 30-min exposure to dirty rat bedding significantly increased plasma corticosterone (CORT) levels and anxiety-related behavior, justifying the use of dirty rat bedding as PS in the subsequent drinking studies. Next, separate groups of male and female C57BL/6J mice received seven binge ethanol sessions (binge) or drank water (controls), followed by a 1-month period of abstinence. Then, 2-bottle choice ethanol intake (10% or 10E vs. water, 23 h/day) was measured in lickometer chambers for 4 weeks. After baseline intake stabilized, exposure to intermittent PS (2x /week x 2 weeks) significantly enhanced ethanol intake after the 2nd PS in male, but not female, binge mice vs. baseline and vs. the increase in controls. However, in a subgroup of females (with low baselines), PS produced a similar increase in 10E intake in control and binge mice vs. baseline. Analysis of lick behavior determined that the enhanced 10E intake in binge male mice and in the female low baseline subgroup was associated with a significant increase in 10E bout frequency and 10E licks throughout the circadian dark phase. Thus, PS significantly increased 10E intake and had a synergistic interaction with prior binge drinking in males, whereas PS produced a similar significant increase in 10E intake in the low baseline subgroup of binge and control females. Plasma CORT levels were increased significantly in both binge and control animals after PS. CORT levels at 24-h withdrawal from daily 10E intake were highest in the groups with elevated 10E licks (i.e., binge males and control females). At 24-h withdrawal, protein levels of GABA(A) receptor al subunit, corticotropin releasing factor receptor 1, and glucocorticoid receptor in prefrontal cortex (PFC) and hippocampus (HC) were differentially altered in the male and female mice vs. levels in separate groups of age-matched na ve mice, with more changes in HC than in PFC and in females than in males. Importantly, the sexually divergent changes in protein levels in PFC and HC add to evidence for sex differences in the neurochemical systems influenced by stress and binge drinking, and argue for sex-specific pharmacological strategies to treat AUG). Published by Elsevier Inc.