|
KMID : 0043320130360070854
|
|
Archives of Pharmacal Research
2013 Volume.36 No. 7 p.854 ~ p.863
|
|
|
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
|
|
Liu Xiaotong
Hong Sung-In
Park Se-Jin
Pena June Bryan dela
Che Haiyan
Yoon Seo-Young
Kim Dong-Hyun
Cai Mudan
Risbrough Victoria
Geyer Mark A.
Shin Chan-Young
Cheong Jae-Hoon
Park Hae-Il
Lew Jae-Hwan
Ryu Jong-Hoon
|
|
|
Abstract
|
|
|
|
We previously reported that oroxylin A, a γ-aminobutyric acid A (GABAA) receptor antagonist, ameliorates drugs-induced memory impairments. We synthesized several oroxylin A derivatives in efforts to find a substance that has pro-cognitive effects as well as improves sensorimotor gating. The aim of the present study is to investigate 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 gating deficit. Memory impairment was induced by scopolamine, a muscarinic receptor antagonist, or MK-801, an N-methyl-d-aspartate receptor antagonist. Sensorimotor gating deficits were 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 cognitive performance of normal animals. Furthermore, DMPC significantly ameliorated MK-801-induced PPI deficits in the acoustic startle response task. In an in vitro study, DMPC (20 μM) inhibited intracellular Cl? influx induced by muscimol, a selective GABAA receptor agonist. These results suggest that DMPC would be a potential candidate for alleviating cognitive dysfunction and sensorimotor gating deficits in schizophrenia, and that its effects may be mediated, in part, via blockade of the GABAergic neurotransmitter system.
|
|
|
KEYWORD
|
|
|
Oroxylin A derivative, Schizophrenia Cognitive dysfunction, Sensorimotor gating deficit
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
  
|
|