Cocaethylene-induced kindling of seizure effects: Cross-specificity with cocaine

Abstract

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.