Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Thurston-Bowles Building, CB#7178, Chapel Hill, NC 27599, USA.
Psychopharmacology (Berl). 2012 Apr;220(4):809-22. doi: 10.1007/s00213-011-2533-8. Epub 2011 Oct 21.
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.
糖皮质激素(例如,重复的压力)的反复和/或升高会促进药物使用行为的加剧,并导致下丘脑-垂体-肾上腺轴功能受损。鉴于内感受/主观药物线索是药物使用行为的一个基本因素,我们试图使用药物辨别技术确定暴露于糖皮质激素皮质酮(CORT)的反复升高对大鼠酒精的内感受效应的影响。
训练雄性长爪沙鼠辨别酒精(1g/kg,IG)与水的长爪沙鼠,暴露于笼内饮用水中的 CORT(300μg/ml),共 7 天。评估了实验者和自我给予酒精的内感受效应,并确定了 HPA 轴功能。
CORT 后,实验者和自我给予酒精的内感受效应减弱。对照实验确定,这种敏感性降低与辨别表现受损或测试时 CORT 水平降低无关,而是依赖于反复的 CORT 暴露。CORT 暴露后 HPA 轴功能受损的易感性提示 CORT 分泌模式改变,以及合成糖皮质激素地塞米松注射后 CORT 反应减弱。
这些发现提出了糖皮质激素升高期间(例如,压力)酒精摄入加剧的可能行为机制。也就是说,在这些情况下,个体可能会摄入更多的酒精来达到期望的内感受效应。了解这些行为机制可能有助于更好地理解促进高危人群中酗酒和滥用酒精的因素。