Anticonvulsant and convulsant effects of cocaine in genetically epilepsy‐prone rats

Abstract

Cocaine produces dose‐dependent increases in locomotor activity which can manifest as seizures at high doses. Cocaine is a local anesthetic that also blocks the uptake of norepinephrine (NE), dopamine (DA) and serotonin (5‐HT). Antidepressants that block the uptake of NE and/or 5‐HT produce anticonvulsant effects in genetically epilepsy‐prone rats (GEPRs) at doses below doses producing seizures. The purpose of this study was to determine if cocaine was capable of producing anticonvulsant effects against sound‐induced seizures in the GEPR. Procaine (local anesthetic) imipramine (NE and 5‐HT uptake blockade) and bupropion (DA uptake blockade) effects were also characterized. Anticonvulsant and convulsant dose response curves were determined in moderate seizure (GEPR‐3s) and severe seizure (GEPR‐9s) GEPRs. Effective dose‐50s for anticonvulsant effects and convulsant dose‐50s were determined for all 4 drugs. Cocaine, procaine, imipramine and bupropion all produced anticonvulsant effects in GEPR‐3s and GEPR‐9s at doses lower than doses producing convulsions. These results suggest that cocaine produces anticonvulsant effects at low doses and convulsant effects at high doses through its local anesthetic and NE, DA and 5‐HT uptake blockade mechanisms.