The ameliorating effects of 5,7-dihydroxy-6-methoxy- 2(4-phenoxyphenyl)-4H-chromene-4-one, an oroxylin A derivative, against memory impairment and sensorimotor gating deficit in mice

We previously reported that oroxylin A, ac-aminobutyric acid A (GABAA) receptor antagonist,ameliorates drugs-induced memory impairments. We synthesizedseveral oroxylin A derivatives in efforts to find asubstance that has pro-cognitive effects as well as improvessensorimotor gating. The aim of the present study is toinvestigate the effect of a novel oroxylin A derivative,5,7-dihydroxy-6-methoxy-2(4-phenoxyphenyl)-4H-chromene-4-one (DMPC), on pharmacological models of schizophrenia,which exhibit memory impairment and sensorimotor gatingdeficit. Memory impairment was induced by scopolamine,a muscarinic receptor antagonist, or MK-801, an N-methyl-Daspartatereceptor antagonist. Sensorimotor gating deficitswere induced by MK-801 and measured by prepulse inhibition(PPI) of the acoustic startle response task. DMPC treatment(20 mg/kg) significantly attenuated scopolamine- or MK-801-induced memory impairment and it even enhanced cognitiveperformance of normal animals. Furthermore, DMPC significantlyameliorated MK-801-induced PPI deficits in theacoustic startle response task. In an in vitro study, DMPC(20 lM) inhibited intracellular Cl- influx induced by muscimol,a selective GABAA receptor agonist. These results suggestthat DMPC would be a potential candidate for alleviatingcognitive dysfunction and sensorimotor gating deficits inschizophrenia, and that its effects may be mediated, in part, viablockade of the GABAergic neurotransmitter system.