Significant controversy exists about the impact of in utero cocaine exposure and postnatal respiratory control. Some authors report altered respiratory patterns as well as an increased incidence of sudden infant death syndrome (SIDS) in infants exposed in utero to cocaine. Others challenge these findings. Most human studies, however, are limited by confounders of polydrug abuse, nutrition, and socio-economic/life style factors. These present studies are designed to investigate the effect of in utero cocaine exposure on postnatal respiratory control in an animal model that controls' for these confounders. Arousal from sleep related apnea is an important component of respiratory control. Our specific hypothesis is that in utero cocaine exposure alters arousal mechanisms to hypoxia and hypercarbia thereby altering postnatal respiratory control particularly during sleep. These alterations may be secondary to altered transmitters in respiratory related nucleis or secondary to a direct neuroteratogenic property of cocaine on brain growth. To test these hypotheses, we will study postnatal respiratory control and arousal in animals exposed in utero to cocaine, in free fed, pair fed, and methoxamine exposed groups. Arousal will be observed behaviorally, the hypoxic and hypercarbic ventilatory responses will be assessed by the barometric method, and the neurotransmitter content of the inhibitory neuropeptide, methionine-enkephalin and the excitatory peptide Substance P will be measured in brainstem nuclei involved in arousal and in respiratory control. Ornithine decarboxylase will be utilized to examine the effect of cocaine on brain growth and the methoxamine group will allow distinction between direct cocaine effect and that of repeated vasoconstrictive and, therefore, hypoxic event. These studies will address the issue of respiratory control abnormalities in infants exposed in utero to cocaine and may provide valuable information about mechanisms operative in SIDS.
