Resilience to the short- and long-term behavioral effects of intermittent repeated social defeat in adolescent male mice

Abstract

Background: 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.

Methods: 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).

Results: 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.

Conclusion: Our findings help to characterize the nature of resilience to the effects of social stress during adolescence.

Keywords: Adolescence; Cocaine; Conditioned place preference; Mice; Resilience; Social defeat stress.