Randall Patrick A, Stewart Robert T, Besheer Joyce
Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7178, USA.
Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7178, USA; Curriculum in Neurobiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7178, USA; Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7178, USA.
Pharmacol Biochem Behav. 2017 May;156:1-9. doi: 10.1016/j.pbb.2017.03.005. Epub 2017 Mar 25.
Alcohol use disorders are a costly public health dilemma. Complicating this issue is the general lack of basic research assessing sex differences in many aspects of alcohol seeking and taking behaviors. The current experiments sought to decrease this gap in our understanding of sex differences in alcohol use disorders by assessing both male and female Long-Evans rats in parallel on alcohol self-administration, relapse-like behavior following abstinence and extinction, and motivation to respond for the standard alcohol solution and a quinine-adulterated alcohol solution. Here, we show that while males tend to have greater alcohol-reinforced responses throughout self-administration training, females show similar or greater alcohol intake (g/kg). Additionally, when tested for reinstatement of alcohol seeking and self-administration, following abstinence or extinction, males consistently showed greater reinstatement responding than females, which may be related to their training history. However, when assessed using the progressive ratio, there were no sex differences in motivation to respond for alcohol. Further, the consistent patterns of responding across months of self-administration training in both males and females, lend support for the feasibility of conducting these studies in male and female rats in parallel without concerns about daily variability. Our data also suggest that males and females should not be pooled as differences in alcohol lever responses and differences in reinstatement, as observed in the current experiments, could affect the overall outcome and possibly confound data interpretation. These studies demonstrate the importance of assessing males and females in parallel and advance the body of preclinical research on sex differences in alcohol self-administration and relapse.
酒精使用障碍是一个代价高昂的公共卫生难题。使这个问题复杂化的是,在寻求和摄取酒精行为的许多方面,普遍缺乏评估性别差异的基础研究。当前的实验旨在通过同时评估雄性和雌性Long-Evans大鼠的酒精自我给药、禁欲和消退后的复发样行为,以及对标准酒精溶液和掺有奎宁的酒精溶液做出反应的动机,来缩小我们在理解酒精使用障碍中性别差异方面的差距。在这里,我们表明,虽然在整个自我给药训练过程中,雄性往往有更强的酒精强化反应,但雌性显示出相似或更高的酒精摄入量(克/千克)。此外,在对禁欲或消退后寻求和自我给药酒精的恢复情况进行测试时,雄性始终比雌性表现出更强的恢复反应,这可能与它们的训练历史有关。然而,当使用累进比率进行评估时,对酒精做出反应的动机没有性别差异。此外,雄性和雌性在数月的自我给药训练中一致的反应模式,支持了在雄性和雌性大鼠中同时进行这些研究的可行性,而无需担心每日变异性。我们的数据还表明,雄性和雌性不应合并,因为在当前实验中观察到的酒精杠杆反应差异和恢复差异可能会影响总体结果,并可能混淆数据解释。这些研究证明了同时评估雄性和雌性的重要性,并推进了关于酒精自我给药和复发中性别差异的临床前研究。