Activation of cannabinoid receptors elicits antidepressant-like effects in a mouse model of social isolation stress.

Social isolation stress (SIS) paradigm is a chronic stress procedure able to induce profound behavioral and neurochemical changes in rodents and evokes depressive and anxiety-like behaviors. Recent studies demonstrated that the cannabinoid system plays a key role in behavioral abnormalities such as depression through different pathways; however, there is no evidence showing a relation between SIS and the cannabinoid system. This study investigated the role of the cannabinoid system in depressive-like behavior and anxiety-like behavior of IC animals. For this purpose, NMRI mice were treated with WIN55, 212-2 (non-selective cannabinoid receptor agonist) and AM-251 (cannabinoid receptor type 1 antagonist) and AM-630 (cannabinoid receptor type 2 antagonist). We found that behavioral abnormality followed by SIS was mitigated after administration of WIN55, 212-2. Also, depressive-like effects induced by SIS were significantly increased following administration of AM-251 and AM-630. Co-administration of cannabinoid receptor antagonists (AM-251 and AM-630), significantly reversed the antidepressant effect of WIN55, 212-2 in IC animals. Our findings suggest that the cannabinoid system is involved in depressive-like behaviors induced by SIS. We showed that activation of cannabinoid receptors (type 1 and 2) could mitigate depression-like behavior induced by SIS in a mouse model.