Evidence that total extract of Hypericum perforatum affects exploratory behavior and exerts anxiolytic effects in rats

Clinical trials have extensively reported the ability of Hypericum perforat um extracts to exert a significant antidepressant activity. Hypericin, the main constituent of H. perforatum extract, is no more regarded as the activ e principle of the antidepressant activity of the drug. Hence, the question of which constituents are involved in the basic activity of the total extr act, is still waiting for an answer. In the present study we focused our at tention on the potential anxiolytic activity of H. perforatum total extract , and of some pure components such as protohypericin and a fraction contain ing hypericin and pseudohypericin. Herein we report that the total extract of H. perforatum increases the locomotor activity in the open field and exe rts anxiolytic activity in the light-dark test, whereas the single componen ts did not show any effect. Interestingly, the anxiolytic activity of the t otal extract was blocked by pretreatment of rats with the benzodiazepine an tagonist Flumazenil, hence suggesting an implication of benzodiazepine rece ptor activation in the anxiolytic effect of H. perforatum extract. Electrop hysiological studies, performed to gain more information on the mechanism o f action, showed that hypericin reduced the GABA-activated chloride current s, while pseudohypericin did an opposite effect. Furthermore, both hyperici n and pseudohypericin inhibited the activation of NMDA receptors. (C) 2000 Elsevier Science Inc.