Proconvulsant and anticonvulsant effects in mice of acute and chronic treatment with cocaine.
The proconvulsant and anticonvulsant effects of acute and chronic exposure to cocaine were investigated in adult, male, CF-1 mice. The proconvulsant effects of cocaine in mice only manifested themselves after daily exposure to motor-stimulant doses. Although daily treatment decreased electroshock convulsion threshold, no motor convulsions were observed. Animals in the proconvulsant state, however, kindled to electrically-induced convulsions more rapidly than did controls. Furthermore, daily treatment with cocaine and electroshock also enhanced the development of electrical kindling. These results illustrate that the excitatory properties of cocaine in the CNS can enhance phenomena which cause a persistent increase in excitability of the CNS. In contrast to the proconvulsant activity after chronic exposure, cocaine, administered acutely, in motor-stimulant doses, was anticonvulsant in a variety of tests using electroshock and chemically-induced convulsions. The drug elevated electroshock thresholds for both minimal and maximal convulsions and these responses were not blocked by haloperidol. In tests for minimal chemically-induced convulsions, cocaine elevated the threshold to N-methyl-DL-aspartate, but not to bicuculline; against maximal convulsions, the drug was anticonvulsant against both N-methyl-DL-aspartate and bicuculline. Cocaine did not affect convulsion thresholds for strychnine, arecoline or aminophylline; these data suggest that the anticonvulsant action of cocaine is relatively selective for the gamma-aminobutyric acid (GABA) and glutamate systems.
Department of Pharmacology, University of Utah School of Medicine, Salt Lake City 84132.
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Karler
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Petty
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Calder
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Turkanis
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants; D003042:Cocaine / Q000494:pharmacology*; D003292:Convulsants; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006220:Haloperidol / Q000494:pharmacology; D007696:Kindling, Neurologic; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D013997:Time Factors
D000927:Anticonvulsants; D003292:Convulsants; D000661:Amphetamine; D003042:Cocaine; D006220:Haloperidol