Clinical reports have indicated that a pregnant woman and her fetus may be subjected to a host of potential problems due to cocaine use. Few studies have examined under controlled laboratory conditions the consequences of cocaine use during pregnancy and, therefore, the effects of cocaine on maternal, fetal and neonatal development and behavior have been poorly documented. This proposal represents plans to continue studies in rhesus monkeys to assess the postnatal consequences of chronic cocaine exposure during gestation. Behavioral, pharmacological and physiological experiments will be performed in young rhesus monkeys previously exposed to cocaine in utero in order to characterize the consequences of prenatal exposure. In addition to defining physical growth characteristics (e.g. body weight, crown-rump length, biparietal diameter, etc.) for cocaine- exposed and pair-fed control subjects, experiments will also be performed to assess the neurobehavioral competence of the monkeys and their responsiveness to cocaine. Three well-established behavioral protocols will be used (delayed matching-to-sample, repeated acquisition and drug self-administration) to test for differences in complex operant performance between drug-exposed and pair-fed control subjects as a function of the gestational age of prenatal exposure and the duration of prenatal exposure. A second set of experiments will be conducted to determine the pharmacokinetic profile of cocaine metabolism in young monkeys previously exposed prenatally to cocaine using HPLC analysis. Finally, prenatally-exposed monkeys will be tested for the effects of cocaine on respiratory function using an established head-plethysmographic technique. For most of these experiments, a full range of doses of cocaine will be studied alone and in combination with other drugs having selective agonist and antagonist actions at various receptors (e.g. dopaminergic, serotonergic, adrenergic, etc.) to determine differences in drug sensitivity among the young monkeys. The prenatally-exposed monkeys will also be monitored and tested for onset of puberty as a measure of the impact of prenatal exposure on the development, maturation and function of the endocrine system (i.e. hypothalamic-pituitary-gonadal axis) controlling reproductive competence. The research will contribute to knowledge of the effects of exposure to cocaine in utero and to the characterization of the rhesus monkey as a model for studying the risks of cocaine use during pregnancy in humans.
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