Fetal behavioral state patterns during and after prolonged exposure to cocaine in sheep

OBJECTIVE: Studies on the effects of cocaine in fetal animals have been limited to acute exposures to the drug. We hypothesized that a prolonged infusion of cocaine to the fetal sheep would initially interrupt normal behavioral state cycling but the effects would be short lived as the fetus gained tolerance to the drug. STUDY DESIGN: The study was performed in a university laboratory on six time-dated pregnant ewes at 125 daysʹ gestation. Fetal sheep, surgically instrumented 3 days before study, were given cocaine hydrochloride 0.6 mg/min for 6 hours. Fetal behavioral state before, during, and after the infusion was compared by repeated-measures analysis of variance. RESULTS: Infusion of cocaine caused a drop in the percentage time that the fetuses spent in both rapid-eye-movement (p< 0.03) and non-raid-eye-movement (p< 0.001) sleep, which was sustained throughout the 6-hour infusion. This was related to a decrease in the number of rapid-eye-movement and non-rapid-eye-movement episodes as opposed to a decreased in the lengths of these behavioral states. With cessation of cocaine infusion, the fetal sheep showed an increase in rapid-eye-movement sleep, with a higher percentage than during control periods (p< 0.02). CONCLUSIONS: Cocaine disrupts fetal rapid-eye-movement sleep without evidence for tolerance to the drug over a 6-hour period. “Catch-up” rapid-eye-movement sleep occurs with cessation of cocaine infusion. Neurobehavioral abnormalities associated with in utero cocaine exposure may be caused by chronic disruption of rapid-eye-movement sleep.