Cannabis vapor self-administration elicits sex- and dose-specific alterations in stress reactivity in rats

Abstract

RationaleCannabis users frequently report stress relief as their primary reason for use. Recent studies indicate that human cannabis users exhibit blunted stress reactivity; however, it is unknown whether this is a cause or a consequence of chronic cannabis use. ObjectivesTo determine whether chronic cannabis vapor self-administration elicits sex- and/or dose-dependent alterations in stress reactivity and basal corticosterone (CORT) concentrations, or whether pre-vapor exposure stress reactivity predicts rates of cannabis vapor self-administration. MethodsMale and female rats were subjected to 30 min acute restraint stress to assess stress reactivity prior to vapor self-administration. Rats were then trained to self-administer cannabis extract vapor containing 69.9% Δ9-tetrahydrocannabinol (THC) at one of four extract concentrations (0, 75, 150, or 300 mg/ml) daily for 30 days. Half of the rats were then subjected to a second restraint stress challenge 24 h after the final self-administration session, while the other half served as no-stress controls. Plasma CORT concentrations were measured prior to stress and immediately post-stress offset. ResultsFemale rats earned significantly more vapor deliveries than male rats. Pre-vapor stress reactivity was not a predictor of self-administration rates in either sex. Basal CORT concentrations were increased following vapor self-administration relative to pre-vapor assessment, irrespective of treatment condition. Importantly, cannabis self-administration dose-dependently reduced stress reactivity in female, but not male, rats. ConclusionsThese data indicate that chronic cannabis use can significantly dampen stress reactivity in female rats and further support the use of the cannabis vapor self-administration model in rats of both sexes.