Neurobehavioural Mechanisms and Endophenotypes of Addictive Behavior Research Unit, Department of Psychobiology, University of Valencia, Valencia, Spain.
Department of Psychology and Sociology, Faculty of Social Sciences, University of Zaragoza, Teruel, Spain.
Pharmacol Biochem Behav. 2023 Jun;227-228:173574. doi: 10.1016/j.pbb.2023.173574. Epub 2023 Jun 12.
Exposure to intermittent repeated social defeat (IRSD) increases the sensitivity of mice to the rewarding effects of cocaine in the conditioned place preference (CPP) paradigm. Some animals are resilient to this effect of IRSD, though research exploring this inconsistency in adolescent mice is scarce. Thus, our aim was to characterize the behavioral profile of mice exposed to IRSD during early adolescence and to explore a potential association with resilience to the short- and long-term effects of IRSD.
Thirty-six male C57BL/6 mice were exposed to IRSD during early adolescence (PND 27, 30, 33 and 36), while another 10 male mice did not undergo stress (controls). Defeated mice and controls then carried out the following battery of behavioral tests; the Elevated Plus Maze, Hole-Board and Social Interaction Test on PND 37, and the Tail Suspension and Splash tests on PND 38. Three weeks later, all the mice were submitted to the CPP paradigm with a low dose of cocaine (1.5 mg/kg).
IRSD during early adolescence induced depressive-like behavior in the Social Interaction and Splash tests and increased the rewarding effects of cocaine. Mice with low levels of submissive behavior during episodes of defeat were resilient to the short- and long-term effects of IRSD. In addition, resilience to the short-term effects of IRSD on social interaction and grooming behavior predicted resilience to the long-term effects of IRSD on cocaine reward.
Our findings help to characterize the nature of resilience to the effects of social stress during adolescence.
间歇性重复社交挫败（IRSD）会增加小鼠对条件性位置偏好（CPP）范式中可卡因奖赏效应的敏感性。尽管针对青少年小鼠的这种 IRSD 效应的研究很少，但有些动物对此具有弹性。因此，我们的目的是描述在青少年早期暴露于 IRSD 的小鼠的行为特征，并探索其与对 IRSD 的短期和长期影响的弹性之间的潜在关联。
36 只雄性 C57BL/6 小鼠在青少年早期（PND 27、30、33 和 36）期间经历 IRSD，而另外 10 只雄性小鼠未经历应激（对照组）。战败小鼠和对照组随后进行了以下行为测试；PND 37 时的高架十字迷宫、洞板和社会互动测试，以及 PND 38 时的悬尾和溅水测试。三周后，所有小鼠都接受了低剂量可卡因（1.5mg/kg）的 CPP 范式。
青少年早期的 IRSD 在社会互动和溅水测试中诱导了类似抑郁的行为，并增加了可卡因的奖赏效应。在战败期间表现出低顺从行为的小鼠对 IRSD 的短期和长期影响具有弹性。此外，对 IRSD 的短期影响的弹性对社会互动和梳理行为的影响预测了对 IRSD 的长期影响对可卡因奖赏的弹性。
我们的发现有助于描述对青少年时期社会压力影响的弹性的本质。
