Effects of Hypericum perforatum (St. John's wort) on passive avoidance in the rat: Evaluation of potential neurochemical mechanisms underlying its antidepressant activity

Along with traditional pharmacotherapies, extracts of Hypericum perforatum L. (St. John's wort) are used in the treatment of mild to moderately severe depression. Hypericum is a nonspecific inhibitor of the neuronal uptake of monoamines (serotonin, 5-HT; noradrenaline, NA; dopamine, DA) as well as G ABA and glutamate. Hypericum extracts have been shown to be active in sever al different "animal models for antidepressant drugs". As one of a large nu mber of chemical constituents, the phoroglucinol derivative hyperforin migh t be an important "antidepressant component" of hypericum. However, the exa ct role of neurochemical mechanisms underlying in vivo actions of hypericum and hyperforin are not well defined. In the present study, we compared the effects of hypericum, hyperforin and hyperforin-free hypericum and the thr ee conventional antidepressants paroxetine, imipramine and desipramine usin g the passive avoidance (PA) task in the rat. The 5-HT-releasing compound p -chloroamphetamine (PCA), which operates through the 5-HT neuronal transpor ter, was used to reveal the potential in vivo effects on 5-HT uptake mechan isms. To examine the ability of the test-compounds to enhance noradrenaline (NA) transmission in vivo, subeffective doses of scopolamine were used. Ta ken together, our results suggest that (1) hypericum given at high doses ca n probably affect the neuronal 5-HT uptake mechanisms in a manner more remi niscent of TCAs than SSRIs, (2) similar to TCAs and SSRls, hypericum and hy perforin are active in the scopolamine test. Hyperforin appears to play a m ajor role in the action of hypericum in this model. Both 5-HT and NA might concomitantly contribute to the effects of different antidepressants in the "low-dose scopolamine" model; (3) hypericum might enhance both 5-HT and NA transmission in forebrain limbic brain circuits important for mood control , which could underly its antidepressant effects. However, the relative con tribution of different constituents and exact mechanisms of action require further evaluation.