Modification of amygdala-kindled postictal inhibition by pentylenetetrazol and diazepam

When fully amygdala-kindled rats are electrically stimulated in grouped trials with intertrial stimulation intervals of less than 60 min, significant residual inhibition can be demonstrated. When these grouped trials of stimulation are repeated daily, additional cumulative inhibition is seen. The present study examined the effect of daily pretreatment with three doses of pentylenetetrazol (5, 10, and 20 mg/kg) and two doses of diazepam (0.5 and 2 mg/kg) on daily, grouped trial electrical stimulations of fully amygdala-kindled rats. Little or no reduction was seen in postictal inhibition by pentylenetetrazol pretreatment including the highest dose tested in which prestimulation bursts of spiking were associated with short episodes of forelimb clonus. Pretreatment with the benzodiazepine receptor agonist, diazepam, resulted in a dose-dependent reduction in the first elicited seizure response each day compared with control trials. Subsequent daily seizure trials of diazepam-treated animals demonstrated a relatively constant degree of dose-dependent seizure suppression without evidence of further postictal inhibition. The neural substrate that governs grouped trial postictal inhibition of amygdala-kindled seizures appears to be resistent to modification by near-convulsant doses of pentylenetetrazol, an agent with a presumed GABA-mediated mechanism of action. Diazepam, an anticonvulsant with a presumed GABA-related or associated mechanism of action, suppressed seizures in a dose-dependent manner nearly equally across all trials.