Department of Psychobiology, Faculty of Psychology, University of Valencia, Blasco Ibañez 21, Valencia, 46010, Spain.
Department of Psychobiology, Faculty of Psychology, University of Valencia, Blasco Ibañez 21, Valencia, 46010, Spain.
Behav Brain Res. 2021 Sep 24;414:113505. doi: 10.1016/j.bbr.2021.113505. Epub 2021 Jul 29.
Cocaine is the most prevalent illegal stimulant drug in Europe among the adult population. Its abuse is characterized by a faster substance abuse disorder (SUD) development than other drugs, with high vulnerability to relapse. However, there does not exist an effective treatment for cocaine dependence. Sex differences have been reported in psychological disorders including SUD. For this reason, it is essential to identify risk factors that predict susceptibility or resilience to cocaine addiction for the development of effective prevention strategies considering sex differences. In the present study, the main objective was to determine more sensitive phenotypes to the conditioned reinforcing effects of cocaine in both sexes. Anxiety-like behavior and the locomotor response to novelty were evaluated in the elevated plus maze, and despair in the tail suspension test, as well as vulnerability traits linked with a high sensitivity to the reinforcing effects of a subthreshold dose of cocaine (1 mg/kg) in the conditioned place preference (CPP) paradigm in male and female mice. Our results indicated that only female mice with high anxiety, low locomotor response to novelty or low despair levels acquired CPP induced by cocaine, while male mice with low anxiety, high locomotor response to novelty or high despair levels presented a higher susceptibility to the rewarding effects of cocaine than others. These sex differences in the results reveal an opposite pattern in males and females on the relationship between anxiety- and depressive-like behaviors and cocaine vulnerability, demonstrating the need to include female mice in preclinical studies.
可卡因是欧洲成年人群体中最常见的非法兴奋剂药物。其滥用的特点是物质使用障碍（SUD）的发展速度比其他药物更快，且容易复发。然而，目前还没有针对可卡因依赖的有效治疗方法。性别的差异在包括 SUD 在内的心理障碍中都有报道。因此，为了制定考虑性别差异的有效预防策略，必须确定预测可卡因成瘾易感性或抗性的风险因素。在本研究中，主要目的是确定在两性中对可卡因条件性增强作用更敏感的表型。焦虑样行为和对新奇事物的运动反应在高架十字迷宫中进行评估，而绝望在悬尾试验中进行评估，以及与亚阈值剂量可卡因（1mg/kg）的增强作用相关的易感性特征在条件性位置偏好（CPP）范式中在雄性和雌性小鼠中进行评估。我们的结果表明，只有焦虑程度高、对新奇事物的运动反应低或绝望程度低的雌性小鼠才会对可卡因诱导的 CPP 产生反应，而焦虑程度低、对新奇事物的运动反应高或绝望程度高的雄性小鼠对可卡因的奖赏作用更敏感。这些结果在焦虑和抑郁样行为与可卡因易感性之间的关系上，在男性和女性之间显示出相反的模式，这表明需要在临床前研究中纳入雌性小鼠。
