Abstract
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.
Highlights
In spite of cumulative evidence of the potential risks of drug abuse, cocaine is widely consumed among adolescents and young adults (European Monitoring Centre for Drugs and Drug Addiction, 2020)
Post-hoc analysis of the Interaction showed a lower percentage of entries into the open arms in the group exposed to maternal separation (MS) and defeat (MS + intermittent repeated social defeat (IRSD)) than mice exposed only to SM (MS + EXPL) or defeat (CONTROL + IRSD)
Post-hoc comparison of the Interaction showed that the group SM + IRSD travelled a shorter distance than the SM + EXPL (p < 0.01) and CONTROL + IRSD (p < 0.05) groups
Summary
In spite of cumulative evidence of the potential risks of drug abuse, cocaine is widely consumed among adolescents and young adults (European Monitoring Centre for Drugs and Drug Addiction, 2020). It is clear that biological factors can predispose an individual to cocaine addiction; different animal models have demonstrated that environmental factors are involved (Badiani and Spagnolo, 2013; El Rawas and Saria, 2016; Montagud-Romero et al, 2018; Ahmed et al, 2020). Among these environmental factors, stress - understood as adversity/negative experiences in life—has been shown to enhance vulnerability to the rewarding effects of cocaine and other drugs of abuse (Aguilar et al, 2013; Rodríguez-Arias et al, 2013; Vannan et al, 2018). Several studies have shown an increase in the rewarding effects of cocaine in the conditioned place preference (García-Pardo et al, 2019; Calpe-López et al, 2020; Montagud-Romero et al, 2020) and self-administration We observed that mice exposed to SD displayed anxiety- and depression-like behaviours, social avoidance and greater stress reactivity (Calpe-López et al, 2020)
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