Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, NC 2759, USA.
Neuropharmacology. 2013 Sep;72:139-47. doi: 10.1016/j.neuropharm.2013.04.036. Epub 2013 May 3.
Stressful life events and chronic stressors have been associated with escalations in alcohol drinking. Stress exposure leads to the secretion of glucocorticoids (cortisol in the human; corticosterone (CORT) in the rodent). To model a period of heightened elevations in CORT, the present work assessed the effects of chronic exposure to the stress hormone CORT on alcohol self-administration. Male Long Evans rats were trained to self-administer a sweetened alcohol solution (2% sucrose/15% alcohol) resulting in moderate levels of daily alcohol intake (0.5-0.7 g/kg). Following stable baseline operant self-administration, rats received CORT in the drinking water for 7 days. A transient increase in alcohol self-administration was observed on the first self-administration session following CORT exposure, and behavior returned to control levels by the second session. Control experiments determined that this increase in alcohol self-administration was specific to alcohol, unrelated to general motor activation, and functionally dissociated from decreased CORT levels at the time of testing. These results indicate that repeated exposure to heightened levels of stress hormone (e.g., as may be experienced during stressful episodes) has the potential to lead to exacerbated alcohol intake in low to moderate drinkers. Given that maladaptive drinking patterns, such as escalated alcohol drinking following stressful episodes, have the potential to put an individual at risk for future drinking disorders, utilization of this model will be important for examination of neuroadaptations that occur as a consequence of CORT exposure in order to better understand escalated drinking following stressful episodes in nondependent individuals.
应激性生活事件和慢性应激源与饮酒量的增加有关。应激暴露会导致糖皮质激素(人类的皮质醇;啮齿动物的皮质酮(CORT))的分泌。为了模拟 CORT 水平升高的时期,本研究评估了慢性暴露于应激激素 CORT 对酒精自我给药的影响。雄性长爪沙鼠被训练自我给予含糖的酒精溶液(2%蔗糖/15%酒精),导致每日酒精摄入量适中(0.5-0.7 g/kg)。在稳定的基线操作自我给药后,大鼠在饮用水中接受 CORT 治疗 7 天。在暴露于 CORT 后的第一次自我给药会议上观察到酒精自我给药的短暂增加,并且在第二次会议时行为恢复到对照水平。对照实验确定,这种酒精自我给药的增加是特定于酒精的,与一般运动激活无关,并且与测试时 CORT 水平降低功能分离。这些结果表明,反复暴露于高水平的应激激素(例如,在应激发作期间可能经历的)有可能导致低至中度饮酒者的酒精摄入量增加。鉴于适应不良的饮酒模式,例如在应激发作后酒精摄入量增加,有可能使个体处于未来饮酒障碍的风险之中,因此利用这种模型对于检查由于 CORT 暴露而发生的神经适应将非常重要,以便更好地理解非依赖个体在应激发作后酒精摄入量增加的情况。