Enhanced antidepressant-like effects of a delta opioid receptor agonist, SNC80, in rats under inflammatory pain.

Depression is a debilitating mental disorder that affects a large population worldwide. Depression and pain comorbidity is well recognized in both clinical and preclinical settings. Research studies suggest delta opioid receptor (DOR) may be involved in modulating pain as well as depression. DOR agonists produce antidepressant-like effects in animal models and their antihyperalgesic effects are enhanced in rats under inflammatory pain. However, it is unclear whether the antidepressant-like effects of DOR agonists may change in the models of pain. In this study, the antidepressant-like effects of a DOR agonist, SNC80, and a tricyclic antidepressant, amitriptyline, were compared following intracerebroventricular (i.c.v.) administration in rats under normal or inflammatory pain state elicited by injection of complete Freund's adjuvant. The forced swim test was used to determine the antidepressant-like effects. Results showed that i.c.v. SNC80 and amitriptyline dose-dependently produced antidepressant-like effects in rats under normal state. The potency of SNC80-induced antidepressant-like effects, but not amitriptyline, was enhanced in rats under inflammatory pain. This study provides functional evidence of the state-dependent effects of DOR agonists and suggests that DOR agonists may be more effective as potential antidepressants for patients experiencing both depression and pain.