Cumulative after-discharge as the principal factor in the acquisition of kindled seizures

The role of after-discharge in the development of behavioral and electrographic seizures (kindling) was evaluated. Rats were stimulated (amygdala) once daily for 10 days 30 min after an intraperitoneal injection of diazepam, phenobarbital, propranolol or vehicle. Following a 10 day period to allow for drug elimination, the daily stimulations (without drug) resumed until all animals responded with fully kindled seizures. Only the lowest dosage groups of diazepam (2 mg/kg) and phenobarbital (15 mg/kg) showed a savings in the number of stimulations to kindle in the non-drug state. This suggests that little or no kindling development had occurred in the drug state with the high doses (4 or 8 mg/kg diazepam, 30 mg/kg phenobarbital). Propranolol treated rats kindled with the same number of stimulations as their control group. As an alternative measure of kindling, the number of seconds of cortical after-discharge accumulated in the drug state, the non-drug state, and the grand total required to kindle were averaged and compared between the drug and control groups. The average grand total number of seconds of after-discharge accumulated by any of the drug or control 188 and 352 sec. None of the grand totals accumulated by any of the drug or control groups differed significantly. The lowest dosage groups treated with diazepam and phenobarbital accumulated significantly less afterdischarge in both the drug and non-drug state than the total for the control. These data suggest that a specific quantity of after-discharge must be elicited to kindle (200-300 sec) and that any after-discharge elicited in the presence of phenobarbital or diazepam will contribute to that quantity.