Effects of hypericum perforatum L. on evoked potentials in guinea pig hippocampal slices

Therapeutic uses of Hypericum extracts have been demonstrated as safe and e ffective in treating mild to moderate depression in numerous clinical trial s. To date, however, no definitive statements on their mode of action can b e made, and little information on their electrophysiological effects is ava ilable. The present communication summarises the results of our efforts dir ected towards clarifying the effects of an ethanolic Hypericum extract (HYP ) and its hydrosoluble fraction (HYPWS), and two of its constituents hyperi cin and hyperforin on electrically evoked population spikes in guinea pig h ippocampal slices. in higher concentrations (> 10 muM), the two extract con stituents tested revealed inhibitory effects only, whereas concentration-de pendent (between 10(-6) to 10(-4) g/l) excitatory effects were observed for HYP and HYPWS. The excitatory effects were strongly amplified by the GABAB antagonist phaclofen, whereas the effects of bicucullin, a GABAA antagonis t, were marginal. The excitations were completely blocked by the AMPA antag onist CNQX, but not by the NMDA antagonists APV and MK801 or the L-type cal cium-channel blocker verapamil. This kind of excitatory effect on the hippo campus is unknown in other antidepressants and; indeed, many of the latter reduce neuronal excitability. We conclude, therefore, that the mechanisms i nvolved in the antidepressant activity of Hypericum extracts are different from those of conventional antidepressants, and that identifying their exci tatory components may facilitate their more rational standardisation.