Cannabinoids and their interactions with diazepam on modulation of serum corticosterone concentration in male mice

Experimental results indicate a mutual interaction between cannabinoidergic and GABAergic systems; however, the interaction between these systems on corticosterone release has not been fully investigated. In this study, we treated male mice with either cannabinoid compounds alone or in combination with diazepam. Blood samples were collected at 60 min post-injection. The serum corticosterone (CORT) level was measured using ELISA technique. Acute treatment of mice by cannabinoid receptor agonist WIN55212-2 (2.5 mg/kg; i.p.) resulted in a significant reduction of CORT, while treatment with either endocannabinoid reuptake inhibitor AM404 or endocannabinoid degradation enzyme inhibitor URB597 increased CORT compared to control group. Co-administration of AM404 or URB597 with cannabinoid CB1 receptor antagonist AM251 blocked the effect of these compounds on CORT. Treatment of mice with different doses of diazepam alone did not alter CORT compared to control group. However, co-administration of diazepam and either AM404 or WIN55212-2 significantly reduced CORT compared to the respective group treated with cannabinoid compound alone. Co-administration of ineffective dose of URB597 and ineffective dose of diazepam increased CORT level compared to groups treated with each compound alone. In conclusion, our findings suggest that the endogenous cannabinoid system is active as a modulator of CORT in mice and diazepam can alter the effect of cannabinoid system in the modulation of neuroendocrine functions.