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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.
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页码:721 / 723
页数:3
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