Department of Neurobiology and Behavior, University of California, Irvine, Irvine, CA, United States of America.
PLoS One. 2019 Jan 31;14(1):e0211346. doi: 10.1371/journal.pone.0211346. eCollection 2019.
Nicotine and cannabis use during adolescence has the potential to induce long lasting changes on affective and cognitive function. Here, we examined whether adolescent exposure to nicotine, the cannabinoid agonist WIN55-212,2 (WIN), or co-exposure to both would alter operant learning, locomotion, and anxiety- and reward-related behaviors in male and female mice during adulthood. Males exposed to a moderate dose of WIN (2 mg/kg) or co-exposed to nicotine and the moderate dose of WIN exhibited decreased anxiety-associated behaviors and increased cognitive flexibility, but did not differ in operant learning or generalized locomotion. In contrast, differences were not found among the females in these measures at the moderate WIN dose or in both sexes with exposure to a low WIN dose (0.2 mg/kg). Furthermore, a sex-dependent dissociative effect was found in natural reward consumption. Males exposed to the moderate dose of WIN or co-exposed to nicotine and the moderate dose of WIN demonstrated increased sucrose consumption. In contrast, females exposed to the moderate dose of WIN exhibited a decrease in sucrose consumption, which was ameliorated with co-administration of nicotine. Together, these novel findings demonstrate that adolescent exposure to cannabinoids in the presence or absence of nicotine results in altered affective and reward-related behaviors during adulthood.
青少年时期使用尼古丁和大麻有可能导致情感和认知功能的持久变化。在这里，我们研究了青春期接触尼古丁、大麻素激动剂 WIN55-212,2（WIN）或两者共同暴露是否会改变成年雄性和雌性小鼠的操作性学习、运动以及焦虑和奖励相关行为。暴露于中等剂量 WIN（2 mg/kg）或同时暴露于尼古丁和中等剂量 WIN 的雄性小鼠表现出焦虑相关行为减少和认知灵活性增加，但在操作性学习或一般运动方面没有差异。相比之下，在中等 WIN 剂量或在暴露于低 WIN 剂量（0.2 mg/kg）的两性中，这些措施在女性中没有发现差异。此外，还发现了自然奖励消耗中的性别依赖性分离效应。暴露于中等剂量 WIN 或同时暴露于尼古丁和中等剂量 WIN 的雄性小鼠表现出蔗糖消耗增加。相比之下，暴露于中等剂量 WIN 的雌性小鼠表现出蔗糖消耗减少，而尼古丁的共同给药可改善这种情况。总之，这些新发现表明，青春期在存在或不存在尼古丁的情况下接触大麻素会导致成年期情感和奖励相关行为发生改变。
