Acute effects of LI 160 (extract of Hypericum perforatum, St John's wort) and two of its constituents on neuroendocrine responses in the rat.

Extracts of Hypericum perforatum (St John's wort), such as LI 160, which are effective antidepressants have several active constituents. Their mode of action in depression, however, is unclear. In the present investigation, we assessed the effect of equivalent doses of LI 160 and two of its components, hypericin and hyperforin on serotonin (5-HT) and dopamine (DA)-mediated neuroendocrine responses in the rat. LI 160, hypericin and hyperforin significantly and equivalently increased plasma corticosterone. This effect was blocked by ketanserin but not WAY-100635, suggesting mediation via 5-HT2 receptors. LI 160 also lowered plasma prolactin and prevented the increase in plasma prolactin following haloperidol administration. Hyperforin had a similar but somewhat less pronounced effect. We conclude that LI 160, hypericin and hyperforin all increase 5-HT-mediated corticosterone release while LI 160 enhances DA-mediated inhibition of prolactin release. Hyperforin may contribute to the facilitatory effect of LI 160 on DA function, but hypericin does not.