NEONATAL VENTILATORY CHANGES FOLLOWING IN-UTERO COCAINE EXPOSURE - A MINIREVIEW OF THE GUINEA-PIG AND RABBIT MODELS

Only three animal studies have been published on the consequences of prenatal cocaine exposure for neonatal ventilation. The one in guinea pigs examines the ventilatory response to carbon dioxide inhalation and two in rabbits consider the response to hypoxia. Cocaine exposure during intrauterine development causes modest and reversible increases in room air breathing and the ventilatory response to carbon dioxide in the neonatal guinea pig. These changes were not dose-dependent over the range studied. Increase of ventilation while breathing room air may be due to drug-related increases in oxygen consumption or neural output. Increased sensitivity to carbon dioxide inhalation, however, is most likely due to an increase in central respiratory drive. Changes in ventilation may be related to persistence of active metabolites or to cocaine withdrawal. In the first published cocaine study in newborn rabbits, ventilation while breathing room air was not altered, whereas the ventilatory response to hypoxia was absent compared to controls. The second study by the same authors, which differed from the first in several respects, again suggested that cocaine did not alter room air breathing in the neonates. A ventilatory response to hypoxia was observed in the cocaine exposed neonates and was even greater than that in control animals. However, the response to severe, prolonged hypoxia in the cocaine-exposed pups was not as effective in maintaining oxygen saturation of blood and heart rate compared to control animals. This finding suggests that total body oxygen consumption and/or cardiovascular function is affected by cocaine in addition to the alteration in ventilation. It is not known if these changes in the rabbit model are reversible or if they are due to persistence of cocaine or active metabolites or cocaine withdrawal. Aspects of study design, statistical analysis and characteristics of the two animal models are compared and contrasted. (C) 1995 Intox Press, Inc.