Modulatory effects of magnolol on potassium-stimulated 5-hydroxytryptamine release from rat cortical and hippocampal slices.

Magnolol, a phenolic constituent of magnolia bark, is a known central nervous system depressant. To examine the possibility that magnolol may elicit its depressant effect by modulating central serotonergic activity, its effect on 35 mM K(+)-stimulated 5-[3H]HT release from rat hippocampal and frontal cortical slices were examined. Inclusion of magnolol (1-100 microM) had no effect on 5-HT release in hippocampal slices but elicited a dose-related inhibition on 5-HT release from cortical slices. The inhibitory effect of magnolol on K(+)-stimulated 5-HT release from the cortex was not affected by either antagonists (metergoline, propranolol, and cyproheptadine) (0.01-10 microM) of various 5-HT receptor subtypes or the voltage-dependent sodium channel blocker tetrodotoxin (1 microM). It is concluded that the suppression of brain 5-HT release by magnolol is site-specific, and the suppression of cortical 5-HT release by magnolol is not via the 5-HT autoreceptors at the 5-HT terminals.