Substance abuse in women of childbearing age involves many different drugs. From among these drugs, cocaine and phencyclidine (PCP) have been selected for this study because each act on the nervous system through different mechanisms and each has potent hypertensive and neurobehavioral effects (the former mediated in part by similar mechanisms) that might cause long- lasting pathologies unique to each compound. Developmental exposure to either drug in utero, via lactation or other methods poses a significant human health risk due to acute cardiovascular (CV) effects and to poorly understood effects on neurobehavioral development. While the mechanisms of deleterious acute and chronic exposure effects of cocaine or PCP are not completely understood, acute exposure to either agent does significantly affect neonatal human, rat and pig behavior and CV function (e.g. hypertension) and therefore has the potential to alter both CV and neurobehavioral development. This proposal tests the hypothesis that neonatal exposure to cocaine or PCP has both acute and long-lasting effects on the central and peripheral nervous systems that result in altered CV and behavioral function during development. The proposed studies will determine acute and chronic postnatal exposure effects of each individual compound on blood pressure (BP), heart rate (HR) and behavior during the neonatal period in rats and pigs. CV responses to feeding will also be measured in chronically treated animals as a potentially useful method for unmasking functional alterations in a biologically significant situation; alterations that may not be apparent under baseline, resting conditions. The rat and pig have been selected for study in part because there is a substantial amount of background data on drug effects in the adult rat and because human and pig CV, digestive and nervous system physiology is very similar. In the acute experiments, exposure effects of cocaine or PCP on BP, HR and behavior will be quantified in unanesthetized neonatal rats and pigs. These studies will characterize the CV and behavioral effects of acute drug exposure and provide dose and control data for the chronic studies. The chronic studies will measure chronic cocaine or PCP exposure effects on the ontogeny of BP, HR behavior and CV responses to feeding in neonatal rats and pigs by determining if each is altered by chronic drug exposure during development. Blood levels of parent compounds and metabolites, catecholamines and corticosterone will be measured in pigs from both studies. This proposal provides a framework in which to study the effects of neonatal drug exposure on the development of CV regulation and behavior. It utilizes an important biological link (the supply of nutrient) between the mother and infant and tests a mechanism by which drugs that alter CV function can disrupt the ontogeny of CV regulation (through altered autonomic function and regulation) and retard growth, behavior and development. Understanding these phenomena will provide information about the underlying causes of pathophysiology and behavioral disorders of the drug-exposed neonate.
| Scalzo, F M; Burge, L J (1995) Cardiovascular effects of cocaine in infant and juvenile piglets. NIDA Res Monogr 158:40-57 |
| Scalzo, F M; Burge, L J (1994) The role of NMDA and sigma systems in the behavioral effects of phencyclidine in preweanling rats. Neurotoxicology 15:191-200 |
| Scalzo, F M; Primozic, S; Burge, L J et al. (1993) Effects of labetalol on cocaine pharmacokinetics in neonatal piglets. Dev Pharmacol Ther 20:54-63 |
| Scalzo, F M; Holson, R R (1992) The ontogeny of behavioral sensitization to phencyclidine. Neurotoxicol Teratol 14:7-14 |
| Scalzo, F M; Burge, L J (1992) The ontogeny of phencyclidine-induced wall climbing and locomotor activity. Dev Psychobiol 25:597-612 |
| Scalzo, F M (1992) Cardiovascular responses to feeding in newborn piglets. Pediatr Res 32:33-8 |
