Calpe-López C, Martínez-Caballero M A, García-Pardo M P, Aguilar M A
Neurobehavioural Mechanisms and Endophenotypes of Addictive Behaviour Research Unit, Department of Psychobiology, University of Valencia, Valencia, Spain.
Department of Psychology and Sociology, Faculty of Social Sciences, University of Zaragoza, Teruel, Spain.
Front Pharmacol. 2022 Mar 11;13:825522. doi: 10.3389/fphar.2022.825522. eCollection 2022.
Exposure to intermittent repeated social defeat (IRSD) increases the vulnerability of mice to the rewarding effects of cocaine in the conditioned place preference (CPP) paradigm. According to the "inoculation of stress" hypothesis, a brief period of maternal separation (MS) can provide protection against the negative effects of IRSD. The aim of the present study was to assess whether exposure to a brief episode of MS prevents the subsequent short-term effects of IRSD on depression- and anxiety-like behaviors and to explore its long-term effects on cocaine CPP in mice. Four groups of male C57BL/6 mice were employed; two groups were separated from their mother [6 h on postnatal day (PND) 9], while the other two groups were not (controls). On PND 47, 50, 53 and 56, mice that had experienced MS were exposed to social defeat in the cage of an aggressive resident mouse (MS + IRSD group) or were allowed to explore an empty cage (MS + EXPL group). The same procedure was performed with control mice that had not experienced MS (CONTROL + IRSD and CONTROL + EXPL groups). On PND57-58, all the mice performed the elevated plus maze and the hole-board, social interaction and splash tests. Three weeks after the last episode of defeat, all the mice underwent the CPP procedure with cocaine (1 mg/kg). Irrespective of whether or not MS had taken place, a reduction in open arms measures, dips, and social interaction was observed in mice that experienced IRSD. A higher latency of grooming and acquisition of cocaine-induced CPP were observed only in mice exposed to IRSD alone (CONTROL + IRSD). These results suggest that exposure to a brief episode of stress early in life increases the subsequent resilience of animals to the effects of social stress on vulnerability to cocaine.
暴露于间歇性重复社会挫败（IRSD）会增加小鼠在条件性位置偏爱（CPP）范式中对可卡因奖赏效应的易感性。根据“应激接种”假说，短暂的母鼠分离（MS）可提供保护，抵御IRSD的负面影响。本研究的目的是评估短暂的MS暴露是否能预防IRSD随后对抑郁样和焦虑样行为的短期影响，并探讨其对小鼠可卡因CPP的长期影响。使用了四组雄性C57BL/6小鼠；两组在出生后第9天（PND9）与母亲分离6小时，而另外两组未分离（对照组）。在PND47、50、53和56天，经历过MS的小鼠在具有攻击性的常驻小鼠笼中遭受社会挫败（MS + IRSD组），或被允许探索空笼（MS + EXPL组）。对未经历过MS的对照小鼠进行相同操作（CONTROL + IRSD和CONTROL + EXPL组）。在PND57 - 58天，所有小鼠进行高架十字迷宫、洞板、社交互动和溅水试验。在最后一次挫败事件三周后，所有小鼠接受可卡因（1 mg/kg）的CPP试验。无论是否发生过MS，经历过IRSD的小鼠在开放臂测量、探洞次数和社交互动方面均减少。仅在单独暴露于IRSD的小鼠（CONTROL + IRSD）中观察到梳理潜伏期延长和可卡因诱导的CPP获得增加。这些结果表明，生命早期暴露于短暂的应激会增加动物随后对社会应激对可卡因易感性影响的恢复力。
