Adolescent cannabinoid type 1 receptor (CB1R) blockade mitigates the effects of adolescent social instability stress (SS) on socially directed behaviour in female rats.

The endocannabinoid system undergoes maturation during adolescence and is involved in the development of social behaviour. In separate studies, we found: (1) that repeated cannabinoid type 1 receptor (CB1R) blockade during adolescence increased social interaction and neuronal activity in the medial prefrontal cortex and nucleus accumbens of female rats, and (2) that adolescent social instability stress (SS; daily 1-h isolation and pairing with a new cage partner from postnatal day (P) 30-45) reduced social interaction and social reward motivation in female rats. Here, we tested the possibility that adolescent CB1R blockade would mitigate the effects of SS on social behavioural deficits in female rats. The CB1R antagonist AM251 (or vehicle) was administered from P30-45 to SS or to non-stressed controls (CTL). AM251 increased social interaction and increased social reward motivation (as measured by a progressive ratio test in a social operant conditioning task) in SS female rats, with no effect in CTLs. To investigate potential molecular correlates of the increased social reward motivation in SS rats treated with AM251, we measured the abundance of signaling proteins within the endocannabinoid, dopamine, and oxytocin systems in the medial prefrontal cortex, nucleus accumbens, and medial amygdala of adult female rats. Neither SS nor AM251 treatment affected protein levels in these regions. Nevertheless, the behavioural results implicate adolescent endocannabinoid signaling as a mechanism through which adolescent social stressors shape social behaviour in female rats.