The effects of repeated corticosterone exposure on the interoceptive effects of alcohol in rats.
The effects of repeated corticosterone exposure on the interoceptive effects of alcohol in rats.
复制标题
重复皮质酮暴露对大鼠酒精内感受作用的影响。
DOI：
10.1007/s00213-011-2533-8
复制
发表时间：
2012-04
影响因子：
3.4
通讯作者：
Hodge CW
中科院分区：
文献类型：
--
作者：
Besheer J;Fisher KR;Grondin JJ;Cannady R;Hodge CW
糖皮质激素重复和/或升高（例如，反复的压力）可以促进升级的吸毒行为并诱导受损的HPA轴功能。考虑到内感受性/主观药物线索是吸毒行为的一个基本因素，我们试图确定暴露于糖皮质激素皮质酮（CORT）的重复升高对酒精的内感受性影响的影响，在大鼠中使用药物歧视技术。将训练辨别酒精（1 g/kg，IG）与水的雄性Long Evans大鼠在饲养笼饮用水中暴露于CORT（300 μg/ml）7天。实验者和自我管理的酒精的内感受性影响进行了评估和HPA轴功能进行了测定。CORT后，实验者和自我给药酒精的内感受性效应减弱。控制实验确定，这种降低的敏感性是无关的歧视性能障碍或降低CORT水平在测试时，是依赖于重复CORT暴露。注射合成糖皮质激素地塞米松后，CORT分泌模式的改变和CORT反应的减弱表明CORT暴露后HPA轴功能受损的易感性。这些发现提出了一种可能的行为机制，即在糖皮质激素升高期间饮酒量增加（例如，应力）。也就是说，在这些发作期间，个体可能会消耗更多的酒精以达到所需的内感受效果。了解这些行为机制可能会导致更好地了解在高危人群中促进酒精中毒和酒精滥用的因素。
Repeated and/or heightened elevations in glucocorticoids (e.g., repeated stress) can promote escalated drug-taking behaviors and induce compromised HPA axis function. Given that interoceptive/subjective drug cues are a fundamental factor in drug-taking behavior, we sought to determine the effects of exposure to repeated elevations in the glucocorticoid corticosterone (CORT) on the interoceptive effects of alcohol in rats using drug discrimination techniques. Male Long Evans rats trained to discriminate alcohol (1 g/kg, IG) vs. water were exposed to CORT (300 μg/ml) in the home cage drinking water for 7 days. The interoceptive effects of experimenter- and self-administered alcohol were assessed and HPA axis function was determined. The interoceptive effects of experimenter- and self-administered alcohol were blunted following CORT. Control experiments determined that this decreased sensitivity was unrelated to discrimination performance impairments or decreased CORT levels at the time of testing and was dependent on repeated CORT exposure. Susceptibility to compromised HPA axis function following CORT exposure was suggested by an altered pattern of CORT secretion and blunted CORT response following injection of the synthetic glucocorticoid dexamethasone. These findings present a possible behavioral mechanism for escalated alcohol drinking during episodes of heightened elevations in glucocorticoids (e.g., stress). That is, during these episodes, individuals may consume more alcohol to achieve the desired interoceptive effects. Understanding these behavioral mechanisms may lead to a better understanding of factors that promote alcoholism and alcohol abuse in at risk populations.