NPI-031G (puerarin) reduces anxiogenic effects of alcohol withdrawal or benzodiazepine inverse or 5-HT2C agonists

被引：41
|
作者：
Overstreet, DH
Kralic, JE
Morrow, AL
Ma, ZZ
Zhang, YW
Lee, DY
机构：
[1] Univ N Carolina, Sch Med, Skipper Bowles Ctr Alcohol Studies, Chapel Hill, NC 27599 USA
[2] Nat Pharmacia Int, Belmont, MA 02178 USA
[3] Harvard Univ, McLean Hosp, Mailman Res Ctr, Belmont, MA 02178 USA
来源：
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR | 2003年 / 75卷 / 03期
关键词：
NPI-031G; alcohol withdrawal; benzodiazepine; GABA(A) and 5-HT2C receptors; social interaction test; anxiety-like behavior; chloride uptake;
D O I：
10.1016/S0091-3057(03)00114-X
中图分类号：
B84 [心理学]; C [社会科学总论]; Q98 [人类学];
学科分类号：
03 ; 0303 ; 030303 ; 04 ; 0402 ;
摘要：
Because extracts of kudzu have been used as a hangover remedy in China for many centuries, we tested the ability of NPI-031G (puerarin), an isoflavone isolated from kudzu, to counteract anxiogenic effects associated with withdrawal from chronic alcohol exposure. NPI-031G (50 and 150 mg/kg ip) significantly increased the social interaction and locomotor activity reduced by withdrawal from 17 days of alcohol (7%) diet. The effects of NPI-031G resembled those of the benzodiazepine antagonist, flumazenil (5 mg/kg), and the 5-HT2C antagonist, SB 242084 (1 mg/kg). In a separate study, control rats were pretreated with NPI-031G (30 min) and then given the anxiogenic compounds DMCM, a benzodiazepine inverse agonist, or Ro 60 0175, a 5-HT2C agonist. NPI-031G significantly counteracted the reduction in social interaction induced by either compound. To identify a potential mechanism of action of NPI-031G, synaptoneurosomes were isolated from the cerebral cortex of untreated rats and chloride uptake assays were carried out. NPI-031G did not have any effect on the stimulation of chloride uptake by muscimol, a GABA(A) agonist. However, it reduced the potentiation of muscimol-stimulated chloride uptake by flunitrazepam, a benzodiazepine agonist, at a concentration of 100 muM. A reduction in [H-3]flunitrazepam binding was also seen at this concentration. These findings are consistent with NPI-031G being a weak benzodiazepine site antagonist. (C) 2003 Elsevier Science Inc. All rights reserved.
引用
收藏
页码：619 / 625
页数：7
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