Investigation of the antidepressant-like effect of dihydroquercetin and the participation of serotonergic mechanisms in the effect

In this study, the antidepressant-like activity potential of the bioactive flavonoid dihydroquercetin (taxifolin) was evaluated by modified forced swimming and tail suspension tests. Dihydroquercetin at a dose of 40 mg/kg showed antidepressant-like activity comparable to fluoxetine by shortening the immobility periods of mice in both tests. p-chlorophenylalanine (p-CPA), an agent that causes serotonin depletion in the central nervous system, was used to investigate the possible involvement of the serotoninergic system in the antidepressant-like activity of dihydroquercetin. p-CPA pre-administrations eliminated the antidepressant-like activity of dihydroquercetin and revealed the critical importance of an intact serotonergic system in the antidepressant-like effect of this phytochemical. In the scope of mechanistic studies, the possible participation of 5-HT1A, 5-HT2A/2C and 5-HT3 receptors in the antidepressant-like activity of dihydroquercetin was investigated using WAY-100635, ketanserin, and ondansetron, respectively. Pre-administration of all three antagonists eliminated the antidepressant-like activity of dihydroquercetin. These findings indicated that the antidepressant-like activity of dihydroquercetin demonstrated in this study was mediated by serotonergic neurotransmission and that 5-HT1A, 5-HT2A/2C, and 5-HT3 serotonergic receptors contributed to this effect. Although the serotonergic system-mediated antidepressant-like activity of dihydroquercetin was demonstrated for the first time in this study, the antidepressant effect of this flavonoid needs to be confirmed with comprehensive efficacy and safety tests on depressed patients.