Potentiating Effect of Glabridin on GABA_A Receptor-Mediated Responses in Dorsal Raphe Neurons

Abstract

Flavonoid-rich ethanol extracts of licorice root have sedative and anxiolytic effects. Glabridin is a major flavonoid component from licorice which we evaluated by examining GABA responses in acutely isolated dorsal raphe neurons of the rat. Neurons were recorded with patch-clamp methods at a holding potential of − 50 mV. Glabridin potentiated GABA-induced responses by positively modulating GABA_A receptor responses with different concentration range. GABA (2 × 10⁻⁶ M)-evoked currents were potentiated in a stepwise pattern increasing glabridin concentration. Between 10⁻¹² and 10⁻⁸ M glabridin increased GABA responses by about 140 % of the control. At concentrations above 10^{− 7} M, a much larger, dose-dependent potentiation occurred before reaching a plateau at 3 × 10⁻⁶ M glabridin. A hypnotic drug, zolpidem, also induced biphasic concentration-potentiation relationship. The glabridin potentiation ratio was 2.2 times larger than the maximum potentiation to the benzodiazepine receptor full agonist diazepam. Benzodiazepine receptor antagonist, flumazenil (3 × 10⁻⁷ M), failed to inhibit glabridin (3 × 10⁻⁷ M)-induced potentiation. This result implies that glabridin may exhibit sedative and hypnotic effects by potentiating GABAergic inhibition in dorsal raphe neurons by GABA_A receptor actions.

Key words

licorice - flavonoid - benzodiazepine receptor - flumazenil - sedative-hypnotic activity - GABA_A receptor - Glycyrrhiza glabra - Fabaceae

• References

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