Sern Kimberly R, Fultz Elissa K, Coelho Michal A, Bryant Camron D, Szumlinski Karen K
Department of Psychological and Brain Sciences, Developmental and Cell Biology, University of California Santa Barbara, Santa Barbara, CA, USA.
Laboratory of Addiction Genetics, Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA, USA.
Subst Abuse. 2020 Jan 20;14:1178221819897073. doi: 10.1177/1178221819897073. eCollection 2020.
Methamphetamine (MA) and alcohol use disorders exhibit a high degree of co-morbidity and sequential alcohol-MA mixing increases risk for co-abuse. Recently, we reported greater MA-conditioned reward in male C57BL/6J mice with a prior history of binge alcohol-drinking (14 days of 2-hour access to 5, 10, 20 and 40% alcohol). As female mice tend to binge-drink more alcohol than males and females tend to be more sensitive than males to the psychomotor-activating properties of MA, we first characterized the effects of binge-drinking upon MA-induced place-conditioning (four pairings of 0.25, 0.5, 1, 2, or 4 mg/kg IP) in females and then incorporated our prior data to analyze for sex differences in MA-conditioned reward. Prior binge-drinking history did not significantly affect locomotor hyperactivity or its sensitization in female mice. However, the dose-response function for place-conditioning was shifted to the left of water-drinking controls, indicating an increase in sensitivity to MA-conditioned reward. The examination of sex differences revealed no sex differences in alcohol intake, although females exhibited greater MA-induced locomotor stimulation than males, irrespective of their prior drinking history. No statistically significant sex difference was apparent for the potentiation of MA-conditioned reward produced by prior binge-drinking history. If relevant to humans, these data argue that both males and females with a prior binge-drinking history are similarly vulnerable to MA abuse and it remains to be determined whether or not the neural substrates underpinning this increased vulnerability reflect common or sex-specific adaptations in reward-related brain regions.
甲基苯丙胺（MA）和酒精使用障碍呈现出高度的共病性，且酒精与MA的顺序混合会增加共同滥用的风险。最近，我们报道了有暴饮酒精史（14天，每天2小时可接触5%、10%、20%和40%酒精）的雄性C57BL/6J小鼠对MA条件性奖赏反应更强。由于雌性小鼠往往比雄性小鼠暴饮更多酒精，且雌性小鼠对MA的精神运动激活特性往往比雄性小鼠更敏感，我们首先研究了暴饮对雌性小鼠MA诱导的位置条件反射（腹腔注射0.25、0.5、1、2或4mg/kg，共配对四次）的影响，然后结合我们之前的数据来分析MA条件性奖赏中的性别差异。既往暴饮史对雌性小鼠的运动性多动或其敏化作用没有显著影响。然而，位置条件反射的剂量反应函数向左移至饮水对照组，表明对MA条件性奖赏的敏感性增加。对性别差异的研究表明，尽管无论既往饮酒史如何，雌性小鼠比雄性小鼠表现出更强的MA诱导的运动刺激，但在酒精摄入量上没有性别差异。既往暴饮史对MA条件性奖赏增强作用没有明显的统计学性别差异。如果这些数据与人类相关，那么这表明有既往暴饮史的男性和女性同样容易滥用MA，而支撑这种易感性增加的神经基质是否反映了奖赏相关脑区的共同适应或性别特异性适应，仍有待确定。
