Hypericum perforatum L (St John's wort) preferentially increases extracellular dopamine levels in the rat prefrontal cortex.

The effects of hydro-alcoholic extracts of Hypericum perforatum L on extracellular serotonin (5-HT), noradrenaline (NA) and dopamine (DA) levels and the acidic metabolites (3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxy-3-indoleacetic acid (5-HIAA)) were examined by in vivo microdialysis in the prefrontal cortex of awake rats. Thus, a single dose (60 mg kg(-1) i.p. or 300 mg kg(-1) p.o.) of H. perforatum increased DA concentrations to 165 and 140% of control values, respectively, and increased locomotor activity in nonhabituated rats. DOPAC and HVA levels were markedly reduced. 5-HT concentrations were elevated only moderately, while the NA levels were not affected by any treatment. The whole-tissue analysis revealed that hypericum increased, whereas the monoamine oxidase (MAO) A/B inhibitor phenelzine decreased DA and 5-HT turnover. The present data indicate that the mechanism of action of hypericum extract in vivo is more complex than the inhibition of monoamine reuptake or metabolism observed in vitro. The finding of preferential enhancement of DA transmission is in agreement with human studies measuring DA-mediated neuroendocrine responses.