Reduction of seizure frequency by clonazepam during cobalt experimental epilepsy

Adult female Sprague-Dawley rats rendered epileptic by bilateral cerebral implantation of cobalt wire were simultaneously prepared with permanent cortical and temporalis muscle electrodes for continuous recording of electroencephalographic (EEG) and electromyographic (EMG) activities. Clonazepam (4, 10 or 40 mg/kg) dissolved in gum acacia was administered once daily intraperitoneally for 5 days beginning 9 days after cobalt implantation. The 40 mg/kg dose completely suppressed generalized seizure activity. Although no tolerance to this effect developed by the fifth day of treatment, generalized seizure activity two days after the last injection was significantly greater in epileptic rats than in control animals. These results suggest that the cobalt model of epilepsy may be useful in the study of mechanisms underlying both anticonvulsant effectiveness and rebound excitability after anticonvulsant drug withdrawal.