Serotonin, norepinephrine and dopamine involvement in the antidepressant action of hypericum perforatum

Hypericum perforatum is considered an effective alternative to the syntheti c antidepressants in the treatment of mild-to-moderate depression. Recently , we showed that the effects on neurotransmitter contents in different brai n regions of laboratory animals are more evident after administration of hy pericum extracts containing a higher concentration of flavonoids, thus sugg esting that these compounds are important in the antidepressant action of h ypericum perforatum. We studied the effects of Ph-50, a hypericum extract s tandardized to flavonoids (50%) and containing 0.3% hypericin and 4.5% hype rforin on brain serotonin content, norepinephrine and dopamine by a high-pe rformance liquid chromatography method in discrete brain areas (cortex, die ncephalon and brainstem) in male Sprague-Dawley rats. Moreover, we evaluate d the effects of Ph-50 alone or in association with sulpiride (a dopamine r eceptor antagonist), metergoline (a serotonin receptor antagonist) and 6-hy droxydopamine (S-OH-DA, destroying norepinephrine-containing neurons) using a forced-swimming test in the rat. Hypericum extract (Ph-50; 250-500 mg/kg ) with acute oral administration enhanced serotonin, norepinephrine and dop amine content in the brain and reduced the immobility time of rats in the f orced-swimming test. Sulpiride, metergoline and 6-OH-DA significantly incre ased the period of immobility in the forced-swimming test for the rats rece iving hypericum extract (Ph-50). The results indicate that the neurotransmi tters studied could be involved in the anti-immobility effects of hypericum , and suggest that its antidepressant action is probably mediated by seroto nergic, noradrenergic and dopaminergic system activation.