Effects of cocaine-induced seizures during pregnancy in the rabbit

The effects of chronic administration of cocaine to pregnant rabbits on maternal seizures and on pregnancy outcome were studied. Cocaine (2, 3 or 4 mg/kg/injection) or saline was administered, I.V., twice daily, from gestation Day 8 (G8) to G29. There were no significant differences in maternal weight gain or pregnancy outcome between saline control animals and animals given a cocaine dose of 2, 3 or 4 mg/kg/injection. Generalized tonic-clonic seizures (GTCSs) were occasionally elicited by the highest dose (4 mg/kg). There were significant individual differences in vulnerability to cocaine-elicited GTCSs in animals given 4 mg/kg/injection. Of this group, 18% were classified as having high vulnerability to seizures, and they experienced a range from 3 to 27 GTCSs. Postnatal mortality of their offspring was significantly increased. The incidence and temporal patterns of GTCSs elicited by chronic, I.V. cocaine in rabbits, at the doses used, are similar to those reported in human cocaine use. These GTCSs may involve different mechanisms from seizures elicited in other animal studies, in which high doses of cocaine are administered I.P. or S.C. Nevertheless, in our animal model, the GTCSs elicited by prenatal cocaine exposure had no detectable effects on pregnancy outcome (except in the highly vulnerable subgroup).