Absence of physiological tolerance to cocaine in pregnant sheep

Objective: To determine whether repetitive administration of cocaine to sheep during pregnancy altered basal hemodynamic states in the mother and fetus, and to determine whether this cocaine exposure would alter subsequent hemodynamic responses to cocaine. Methods: Cocaine or saline was administered to 16 pregnant sheep daily from day 75 to day 128 of gestation (term = 145 days). At 128 days' gestation, maternal and fetal basal physiological measurements, including organ-specific blood flow in the fetus, were determined. Each experimental and control ewe then received cocaine 2 mg/kg and these physiological parameters were again measured over the next 30 min to determine whether the experimental animals had developed tolerance to the effects of cocaine. Results: No differences were seen in basal physiological parameters between treatment groups. Likewise, following an acute administration of cocaine, physiological parameters in both groups responded in a similar fashion. Fetal hypoxemia occurred in both groups after the ewe received cocaine. In response to hypoxemia, whether it was the animals' first or 53rd exposure to cocaine, fetal cerebral, myocardial and adrenal blood flow increased so that oxygen delivery was unimpaired. Conclusions: For the cardiovascular parameters measured in this study, we found no tolerance to cocaine in the ewe or fetus. The acute hemodynamic effects of maternal cocaine administration were as severe for animals having received it more than 50 times as for those that received it for the first time.