Sey Nancy Y A, Gómez-A Alexander, Madayag Aric C, Boettiger Charlotte A, Robinson Donita L
Bowles Center for Alcohol Studies, University of North Carolina, Chapel Hill, NC, USA; Neuroscience Curriculum, University of North Carolina, Chapel Hill, NC, USA.
Bowles Center for Alcohol Studies, University of North Carolina, Chapel Hill, NC, USA.
Behav Brain Res. 2019 Nov 5;373:112085. doi: 10.1016/j.bbr.2019.112085. Epub 2019 Jul 15.
Alcohol exposure is linked to behavioral flexibility deficits in humans, but it is unclear when the critical exposure occurred or if alcohol exposure alone is sufficient to produce behavior deficits. Increasing evidence shows that binge levels of alcohol during adolescence are particularly harmful to the brain, producing physiological and behavioral effects that can persist into adulthood. The present study determined whether adolescent intermittent ethanol (AIE) in rats impaired action selection in a discriminative stimulus task using a foraging response. Rats were exposed to ethanol during adolescence (5 g/kg/day, IG, 2-days-on/2-days-off, postnatal day 25-54). In adulthood, they learned to dig for food reward buried in one of two media, cued with one of two odors. AIE and control rats both learned to discriminate between olfactory cues, but AIE rats were impaired when reversing that learned association (first intra-dimensional reversal). However, AIE rats were faster to reinstate the original odor discrimination rule (second reversal), suggesting perseverative behavior. Next, the reward location was cued by digging media rather than odor. Both groups learned this extra-dimensional shift; however, control rats were slower to reach criterion. These findings are consistent with studies of people with substance abuse disorder, who learn new stimulus-response associations similarly to, or better than, control subjects, but perseverate when attempting to replace a well-learned association. These data suggest that adolescent binge-alcohol exposure contributes to behavioral flexibility deficits observed in adulthood.
酒精暴露与人类行为灵活性缺陷有关，但尚不清楚关键暴露发生的时间，也不清楚仅酒精暴露是否足以产生行为缺陷。越来越多的证据表明，青少年时期的暴饮水平酒精对大脑特别有害，会产生持续到成年期的生理和行为影响。本研究确定了大鼠青春期间歇性乙醇（AIE）暴露是否会在使用觅食反应的辨别性刺激任务中损害动作选择。大鼠在青春期暴露于乙醇（5克/千克/天，灌胃，2天给药/2天停药，出生后第25 - 54天）。成年后，它们学会挖掘埋在两种介质之一中的食物奖励，由两种气味之一提示。AIE组和对照组大鼠都学会了区分嗅觉线索，但在逆转这种习得的关联（第一次维度内逆转）时，AIE组大鼠受损。然而，AIE组大鼠恢复原来气味辨别规则（第二次逆转）的速度更快，表明存在固执行为。接下来，奖励位置由挖掘介质而不是气味提示。两组都学会了这种维度外转换；然而，对照组大鼠达到标准的速度较慢。这些发现与物质滥用障碍患者的研究一致，他们学习新的刺激 - 反应关联与对照组相似或更好，但在试图取代一个已牢固习得的关联时会固执己见。这些数据表明，青少年暴饮酒精暴露会导致成年期出现行为灵活性缺陷。
