title: Potentiating effect of glabridin on GABAA 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 GABAA 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 GABAA receptor actions.
authors: Department of Physiology, School of Medicine, Kyung Hee University, Seoul, Republic of Korea.
authors: Zhenhua
authors: Z
authors: Jin
authors: Sojin
authors: S
authors: Kim
authors: Suengmok
authors: S
authors: Cho
authors: In-Ho
authors: IH
authors: Kim
authors: Daeseok
authors: D
authors: Han
authors: Young-Ho
authors: YH
authors: Jin
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003975:Diazepam / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005442:Flumazenil / Q000494:pharmacology; D018682:GABA Agents / Q000494:pharmacology*; D006035:Glycyrrhiza / Q000737:chemistry*; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D007529:Isoflavones / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010424:Pentobarbital / Q000494:pharmacology; D010636:Phenols / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology*; D018517:Plant Roots; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism*; D000077334:Zolpidem; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
chemical_list: D014151:Anti-Anxiety Agents; D018682:GABA Agents; D006993:Hypnotics and Sedatives; D007529:Isoflavones; D010636:Phenols; D010936:Plant Extracts; D011725:Pyridines; D011963:Receptors, GABA-A; D005442:Flumazenil; D005680:gamma-Aminobutyric Acid; D000077334:Zolpidem; C107601:glabridin; D010424:Pentobarbital; D003975:Diazepam