GLUTAMATE RECEPTOR ANTAGONISTS BLOCK COCAINE-INDUCED CONVULSIONS AND DEATH

被引:44
作者
ROCKHOLD, RW [1 ]
ODEN, G [1 ]
HO, IK [1 ]
ANDREW, M [1 ]
FARLEY, JM [1 ]
机构
[1] UNIV MISSISSIPPI,MED CTR,DIV BIOSTAT,JACKSON,MS 39216
关键词
COCAINE; MICE; MK-801; DEXTRORPHAN; GLUTAMATE RECEPTORS; CONVULSIONS;
D O I
10.1016/0361-9230(91)90052-L
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The involvement of excitatory amino acid (EAA) receptors in mediation of the toxic effects of cocaine was studied in male ICR mice. Cocaine HCI (90 mg/kg, IP) induced seizures in 95% and death within 24 h in 68% (n = 135) of the animals. There was a significant correlation (r = .54) between the time to onset of convulsions and the time to death in mice which died within 30 min of injection (n = 84). Pretreatment with selected EAA receptor antagonists 15 min prior to cocaine differentially blocked cocaine toxicity. Selective N-methyl-D-aspartic acid (NMDA) receptor antagonists (MK-801, dextrorphan, CPP) decreased both the incidence of seizures and mortality. A nonselective EAA antagonist, kynurenic acid, decreased lethality in doses which did not reduce convulsions. A similar action was observed following pretreatment with the selective kainic acid/AMPA receptor antagonist, GDEE. Antagonists at EAA receptors can provide significant protection against cocaine-induced toxicity. Moreover, the data provide evidence for the involvement of both NMDA and non-NMDA receptor subtypes in aspects of cocaine toxicity.
引用
收藏
页码:721 / 723
页数:3
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