Glutamate receptor antagonists block cocaine-induced convulsions and death

• Published in: Brain research bulletin Vol. 27; no. 5; p. 721
• Main Authors: Rockhold, R W, Oden, G, Ho, I K, Andrew, M, Farley, J M
• Format: Journal Article
• Language: English
• Published: United States 01-11-1991
• Subjects: 6-Cyano-7-nitroquinoxaline-2,3-dione; Animals; Anticonvulsants - pharmacology; Cocaine - toxicity; Death; Dextrorphan - pharmacology; Dizocilpine Maleate - pharmacology; Dose-Response Relationship, Drug; Glutamates - metabolism; Glutamates - pharmacology; Kynurenic Acid - pharmacology; Male; Mice; Mice, Inbred ICR; Piperazines - pharmacology; Quinoxalines - pharmacology; Receptors, Glutamate; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors; Receptors, Neurotransmitter - antagonists & inhibitors; Receptors, Neurotransmitter - physiology; Seizures - chemically induced; Seizures - prevention & control; Time Factors
• ISSN: 0361-9230
• DOI: 10.1016/0361-9230(91)90052-L

The involvement of excitatory amino acid (EAA) receptors in mediation of the toxic effects of cocaine was studied in male ICR mice. Cocaine HCl (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.