Ketamine-induced changes in kindled amygdaloid seizures

The effects of ketamine on seizures kindled by repetitive electrical stimulation of the amygdala were determined in the rat. The response of fully developed kindled amygdaloid seizures (KAS) to 20, 40, 80 and 120 mg/kg (i.p.) ketamine, administered from 5 to 60 min prior to elicitation of seizures was examined. Ketamine reduced the afterdischarge duration (AD) and behavioral response (BR) in a dose-dependent fashion. However, the effect of ketamine on the afterdischarge duration and behavioral response was not clearly time-dependent for each dose (20–120 mg/kg). A dose-dependent increase in the seizure spiking frequencies in the amygdala and cortex during kindled amygdaloid seizures was also induced by ketamine. Blood plasma and brain levels of ketamine and its metabolites were determined 15 min after 20, 40, 80 and 120 mg/kg ketamine as well as 60 min after 80 mg/kg ketamine. Brain and plasma levels of ketamine and nor-ketamine were similar to those previously reported. Low plasma levels of dehydro-nor-ketamine were seen only at 60 min after 80 mg/kg ketamine. The decrease in afterdischarge duration and behavioral response and the increase in afterdischarge duration spiking frequency seen at 15 min correlated with elevated levels of ketamine and nor-ketamine in brain and plasma. However, by 60 min plasma levels of ketamine remained high, yet the brain levels of both ketamine and nor-ketamine had decreased. This is despite the fact that afterdishcarge duration and behavioral response were still attenuated and afterdischarge duration spiking frequency was still increased. Thus, the exact contribution by ketamine and nor-ketamine to the alteration of afterdischarge duration, behavioral response and afterdischarge spiking frequency cannot be made at this time. It was apparent that inhibition of the afterdischarge duration and behavioral response along with an increase in spiking frequency was not dependent on dehydro-nor-ketamine. The possibility that an unidentified metabolite may contribute to the modification of kindled amygdaloid seizures by ketamine is discussed.