Matthews Douglas B, Scaletty Samantha, Trapp Sarah, Schreiber Areonna, Rossmann Gillian, Imhoff Bailey, Petersilka Quinn, Kastner Abigail, Pauly Jim, Nixon Kimberly
Department of Psychology, University of Wisconsin-Eau Claire, Eau Claire, WI, United States.
Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY, United States.
Front Behav Neurosci. 2023 Aug 1;17:1223883. doi: 10.3389/fnbeh.2023.1223883. eCollection 2023.
Binge-like ethanol exposure during adolescence has been shown to produce long lasting effects in animal models including anxiety-like behavior that can last into young adulthood and impairments in cognition that can last throughout most of the lifespan. However, little research has investigated if binge-like ethanol exposure during adolescence produces persistent anxiety-like behavior and concomitantly impairs cognition late in life. Furthermore, few studies have investigated such behavioral effects in both female and male rats over the lifespan. Finally, it is yet to be determined if binge-like ethanol exposure during adolescence alters microglia activation in relevant brain regions late in life. In the present study female and male adolescent rats were exposed to either 3.0 or 5.0 g/kg ethanol, or water control, in a chronic intermittent pattern before being tested in the elevated plus maze and open field task over the next ∼18 months. Animals were then trained in a spatial reference task via the Morris water maze before having their behavioral flexibility tested. Finally, brains were removed, sectioned and presumptive microglia activation determined using autoradiography for [H]PK11195 binding. Males, but not females, displayed an anxiety-like phenotype initially following the chronic intermittent ethanol exposure paradigm which resolved in adulthood. Further, males but not females had altered spatial reference learning and impaired behavioral flexibility late in life. Conversely, [H]PK11195 binding was significantly elevated in females compared to males late in life and the level of microglia activation interacted as a function of sex and brain regions, but there was no long-term outcome related to adolescent alcohol exposure. These data further confirm that binge-like ethanol exposure during adolescence produces alterations in behavior that can last throughout the lifespan. In addition, the data suggest that microglia activation late in life is not exacerbated by prior binge-like ethanol exposure during adolescence but the expression is sex- and brain region-dependent across the lifespan.
在动物模型中，青春期期间暴饮暴食式的乙醇暴露已被证明会产生长期影响，包括持续到青年期的类似焦虑行为，以及持续一生大部分时间的认知障碍。然而，很少有研究调查青春期期间暴饮暴食式的乙醇暴露是否会产生持续的类似焦虑行为，并同时在晚年损害认知。此外，很少有研究在雌性和雄性大鼠的整个生命周期中调查这种行为影响。最后，青春期期间暴饮暴食式的乙醇暴露是否会在晚年改变相关脑区的小胶质细胞激活尚待确定。在本研究中，雌性和雄性青春期大鼠以慢性间歇性模式暴露于3.0或5.0 g/kg乙醇或水对照中，然后在接下来的约18个月内在高架十字迷宫和旷场试验中进行测试。然后通过莫里斯水迷宫对动物进行空间参考任务训练，之后测试它们的行为灵活性。最后，取出大脑，切片，并使用[H]PK11195结合的放射自显影法确定推测的小胶质细胞激活情况。雄性而非雌性在慢性间歇性乙醇暴露范式后最初表现出类似焦虑的表型，这种表型在成年期消失。此外，雄性而非雌性在晚年出现空间参考学习改变和行为灵活性受损。相反，与雄性相比，雌性在晚年[H]PK11195结合显著升高，小胶质细胞激活水平随性别和脑区而变化，但与青春期酒精暴露没有长期关联。这些数据进一步证实，青春期期间暴饮暴食式的乙醇暴露会导致行为改变，这种改变可能会持续一生。此外，数据表明，青春期期间先前暴饮暴食式的乙醇暴露不会加剧晚年小胶质细胞的激活，但这种表达在整个生命周期中依赖于性别和脑区。
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