Adolescent CB1 receptor expression at the BLA and CA1 and acute AM251 effects on sociability and emotional memory are sex-specific, and not modulated by heterotypic stress exposure

Abstract

Blockade of endocannabinoid CB1R has shown effects on adulthood sociability, memory and fear responses, under basal and stress conditions. In this study, we examined sex-specific effects of exposure to heterotypic stress in the prepubescent period, marked by maturation of brain systems, on endocannabinoid receptors expression, corticosterone secretion and effects of CB1 receptor blockade on social and cognitive responses. Sixty-four (N = 32 per sex) adolescent male and female rats were randomly assigned to a stress or no stress condition. Rats in the stress condition underwent a 10-day heterotypic stress paradigm alternating between restraint stress and forced swim exposure occurring between postnatal day (PND) 30 and PND39. On PND42 and PND44, rats pretreated with the cannabinoid 1 receptor (CB1) antagonist AM251 (1 mg/kg; i.p.) or a vehicle solution underwent behavioural testing in the social interaction and the Y-Maze passive avoidance tests. Our findings indicated acute CB1 antagonism to reduce sociability and fear memory, independently of sex or stress. Notably, baseline and stress-related corticosterone (CORT) detection indicated adolescent male to more rapidly habituate to stress exposure than female rats. Male rats also showed increased CB1 receptor expression at the basolateral amygdala and CA1 regions, although GR-ir remained unaltered. Together, our findings support observed sex- and region- specific differences in CB1 receptor expression during the adolescence period to be minimally influenced by prior heterotypic stress exposure.