Cocaethylene-induced kindling of seizure effects: cross-specificity with cocaine.
Sensitization and cross-sensitization to the seizurogenic effects of cocaine and cocaethylene were examined in the HS strain of mice. Animals were administered IP injections of either 48 mg/kg cocaine or 32 mg/kg cocaethylene once per day for 4 days. On the fifth day, mice were injected with either the same drug that was administered on days 1-4 or the alternative psychostimulant and the occurrence of seizure activity was recorded. Repeated cocaine administration resulted in the induction of tonic-clonic seizures and status epilepticus in 90% of the animals tested with cocaine on the fifth day. A similar increase in seizure prevalence, noted as a kindling effect, was observed in cocaethylene-treated animals tested with cocaethylene in that 90% of the mice exhibited status epilepticus on the last test day. Significant cross-sensitization was observed only in the group that received cocaethylene following repeated cocaine exposure. However, data obtained from animals injected with cocaine following cocaethylene treatment also were suggestive of cross-sensitization effects. Results are discussed in terms of the potential mechanistic differences between cocaine and its ethanol-derived product, as well as its relevance to cocaine use/abuse.
Meehan
S M
SM
Northeastern Ohio Universities, College of Medicine, Rootstown 44272, USA.
Schechter
M D
MD
D000818:Animals; D003042:Cocaine / Q000031:analogs & derivatives* / Q000494:pharmacology; D003292:Convulsants / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004347:Drug Interactions; D004830:Epilepsy, Tonic-Clonic / Q000139:chemically induced; D005260:Female; D007696:Kindling, Neurologic / Q000187:drug effects*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D012640:Seizures / Q000139:chemically induced*; D013226:Status Epilepticus / Q000139:chemically induced
D003292:Convulsants; D018765:Dopamine Uptake Inhibitors; C066444:cocaethylene; D003042:Cocaine