Doremus-Fitzwater Tamara L, Spear Linda P
Center for Developmental Psychobiology, Department of Psychology, Binghamton University, Binghamton, New York, USA.
Alcohol Clin Exp Res. 2007 Sep;31(9):1516-27. doi: 10.1111/j.1530-0277.2007.00457.x.
Withdrawal from an acute high ethanol dose induces behaviors reminiscent of withdrawal from chronic ethanol exposure. While such "hangover"-related anxiety has previously been shown to be considerably less pronounced in adolescent compared to adult male rats, ontogenetic studies are limited and few experiments have directly compared sex- and age-related differences in sensitivity to ethanol hangover.
The current experiments examined consequences of a previous ethanol challenge (4.0 g/kg i.p. injection, 20% v/v) on anxiety and exploratory behavior in the elevated plus-maze (EPM) and holeboard (HB) tests, respectively, in adolescent and adult male and female Sprague-Dawley rats.
In Exp. 1, evidence of hangover-related anxiety and withdrawal-induced hypoactivity emerged at both ages and in both sexes. As several procedural variables were changed in Exp.1 relative to previous studies from our laboratory showing age-related differences in these hangover measures, Exp. 2 explored the possible contribution of 2 variables to ontogenetic expression of withdrawal-induced anxiogenesis: (1) isolation vs. social context during the postchallenge recovery period and (2) EPM testing alone or immediately following a 5 minute HB test. Results of Exp. 2 revealed few significant interactions of these variables with age- and ethanol exposure-related anxiety measures, although sequential testing (HB before EPM) notably suppressed activity in the EPM and altered the major underlying component of EPM behavior from anxiety to activity as revealed in factor analyses of these data. Additional analyses conducted on animals tested only in the EPM revealed attenuations in withdrawal anxiogenesis among adolescents, along with withdrawal-related decreases in activity at both ages.
Taken together, these results suggest that adolescents do show an attenuated sensitivity to hangover-induced anxiogenesis in the EPM, an age difference not evident under other pretest conditions. Therefore, caution should be exerted when using the EPM to index anxiety across age. The robustness of withdrawal-related hypoactivity at both ages suggests that adolescents may not be globally insensitive to the consequences of previous binge-like exposure to ethanol, but rather less likely to express certain hangover-related consequences.
从急性高剂量乙醇中戒断会引发一些行为,这些行为让人联想到从慢性乙醇暴露中戒断的情况。虽然此前已表明,与这种“宿醉”相关的焦虑在青春期雄性大鼠中比成年雄性大鼠中要明显轻得多,但个体发育研究有限,很少有实验直接比较了对乙醇宿醉敏感性的性别和年龄差异。
当前实验分别在高架十字迷宫(EPM)和洞板(HB)试验中,检测了先前乙醇激发(腹腔注射4.0 g/kg,20% v/v)对青春期和成年雄性及雌性斯普拉格-道利大鼠焦虑和探索行为的影响。
在实验1中,两个年龄段和两种性别的大鼠均出现了与宿醉相关的焦虑和戒断诱导的活动减少的证据。由于相对于我们实验室之前显示这些宿醉指标存在年龄差异的研究,实验1中改变了几个程序变量,实验2探究了两个变量对戒断诱导的焦虑发生个体发育表达的可能影响:(1)激发后恢复期的隔离与社交环境,以及(2)单独进行EPM测试或在5分钟HB测试后立即进行EPM测试。实验2的结果显示,这些变量与年龄和乙醇暴露相关的焦虑指标之间几乎没有显著的相互作用,尽管顺序测试(先进行HB测试再进行EPM测试)显著抑制了EPM中的活动,并如这些数据的因子分析所示,将EPM行为的主要潜在成分从焦虑转变为活动。对仅在EPM中测试的动物进行的额外分析显示,青春期大鼠戒断焦虑发生有所减轻,两个年龄段的大鼠在戒断时活动均减少。
综合来看,这些结果表明,青春期大鼠在EPM中对宿醉诱导的焦虑发生确实表现出较低的敏感性,这种年龄差异在其他预测试条件下并不明显。因此,在使用EPM来评估不同年龄的焦虑时应谨慎。两个年龄段大鼠戒断相关活动减少的稳健性表明,青春期大鼠可能并非对先前类似暴饮的乙醇暴露后果完全不敏感,而是不太可能表现出某些与宿醉相关的后果。