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.
Baraban
S C
SC
Department of Neurological Surgery, University of Washington, Seattle 98195, USA. bara@u.washington.edu
McCarthy
E B
EB
Schwartzkroin
P A
PA
D000818:Animals; D003042:Cocaine / Q000633:toxicity*; D004198:Disease Susceptibility; D004558:Electric Stimulation; D004569:Electroencephalography / Q000187:drug effects*; D005260:Female; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D012640:Seizures / Q000139:chemically induced*
D003042:Cocaine