The Noradrenergic System is Partly Involved in Resveratrol Antidepressant and Anti-Obsessive Like Effects in Mice Model

Background and objectives: Resveratrol is a natural phenol in food particularly the skin of fruits like red grapes. It has been shown to have biological, and antidepressant effects. The objective of the present study was to evaluate the role of adrenergic system on antidepressant and anti-obsessive effect of resveratrol. Methods: Male mice (weighing 27±2 g) were used. A tyrosine hydroxylase inhibitor, α-methyl-p-tyrosine (AMPT 100 mg/kg), α1 adrenergic receptors (AR) antagonist (prazosin, 1 mg/kg), α2-AR antagonist (yohimbine, 1 mg/kg), β-AR antagonist (propranolol, 2 mg/kg) and a tricyclic antidepressant (imipramine, 5 mg/kg), were injected before resveratrol (60 mg/kg). Locomotor activity, burring behavior during marble burring test, and immobility time during forced swimming test (FST) were evaluated. Results: No significant difference was observed in the locomotor activity between groups. The immobility time increased following pretreatment with AMPT (147.3±6.35s vs resveratrol alone 85.67±4.51s, p<0.001); marble burring behavior also increased significantly, indicating the possible role of norepinephrine in resveratrol antidepressant and anti-obsessive-like effects. Propranolol (163.8±8.25 s, p<0.001) and yohimbine (151.0±6.47s, p=0.0030) pretreatment also increased immobility in the FST compared to resveratrol. Pretreatment with prazosin did not cause important change in FST. Pretreatment with propranolol slightly increased marble burring behavior while no changes were observed following yohimbine or prazosin administration. Imipramine pretreatment did not have additive antidepressant effect with resveratrol and increased immobility time (136.1±16.88 s, p=0.014 vs resveratrol). Conclusion: Resveratrol antidepressant-like effect is partly mediated by the noradrenergic system, and by interaction with β-AR and α2-AR. Additionally, resveratrol anti-obsessive-like property involves noradrenergic system but not the β or α-AR.