Evidence for increased seizure susceptibility in rats exposed to cocaine in utero.

Clinical observations indicate that cocaine use during pregnancy is a major health concern in the United States and may result in seizure-like behavior in the offspring. In the present study, we investigated whether prenatal cocaine exposure altered seizure thresholds measured in Sprague-Dawley rats, 60-90 days postnatal. In vitro postnatal studies, focusing on hippocampal tissue, revealed a reduced threshold for both electrical stimulation- and potassium-induced epileptiform discharges in slices from cocaine-exposed animals. Modest elevation of extracellular potassium concentration from 3 to 6 mM KCl elicited spontaneous epileptiform discharges in the majority of slices from cocaine-exposed animals (13/20) but rarely in slices from saline-exposed animals (2/18). In vivo studies on awake, freely behaving adult rats indicated a significant reduction in thresholds for both flurothyl- and kainic acid-induced seizures in cocaine-exposed animals. Video-EEG monitoring during administration of kainic acid revealed reduced latencies to first 'electrographic seizure' and first 'electrographic seizure with behavior' in rats exposed to cocaine in utero compared to saline-treated controls. These studies provide strong experimental evidence that adult animals exposed to cocaine during gestation are at high risk for the development of seizure activity.