Chrysin enhances serotonergic and noradrenergic neurotransmission associated with antidepressant effects: A pharmacological study

The aim of this study was to investigate the potential antidepressant-like effect of combined subthreshold and effective doses of chrysin and fluoxetine in adult male Wistar rats and their potential effects on the serotonergic and noradrenergic systems. Seventy rats were divided into seven experimental groups: vehicle (10 % dimethyl sulfoxide solution, DMSO), chrysin (4 or 20 µmol kg^–1), fluoxetine (1.6 and 3.2 µmol kg^–1), and their combinations. The treatments were administered for 28 consecutive days, and the effects were evaluated in the locomotor activity test (LAT) and forced swim test (FST). The results showed that the treatments did not significantly affect crossings in the LAT. Chrysin, alone or combined, reduced immobility time, increased latency to first immobility and prolonged swimming in the FST, similar to fluoxetine. However, only chrysin (20 µmol kg^–1) and its combination with fluoxetine (1.6 µmol kg^–1) enhanced climbing behaviour in the FST. Chrysin showed an anti-depressant effect, possibly related to enhanced serotonergic and noradrenergic neurotransmission, by increasing climbing and swimming time in the FST. This dual effect suggests a promising antidepressant prototype with different mechanisms of action, allow ing the use of subthreshold doses, which could reduce side effects.