Very little is known about the effects of cocaine on the developing child, when exposed in utero. The dearth of data is more recently being added to by anectodotal, small group or clinical case reports of neonates born to cocaine abusers who also invariably are polydrug abusers. This makes it difficult or impossible to separate direct from indirect effects, as well as effects due solely or primarily to cocaine exposure, except in those instances where clearcut acute toxic manifestations are responsible (e.g. subdural hematoma or other evidence of CVA or seizures). Even then, combinations of multiple drug exposure, poor nutritional or health status (i.e. infectious hepatitus due to i.v. drug self-administration) may be more responsible for morbidity/mortality of cocaine-exposed neonates. This proposal requests funds for studying the effects of cocaine, administered at different doses, via different routes, to pregnant rats (prior to and throughout pregnancy or at different stages of pregnancy) or to breeder male rats in order to assess the neurobehavioral consequences of such exposure. Measures will include CNS excitability, using spontaneous and evoked EEG and spontaneous behaviors of conscious rats implanted with telemetric devices for 24 hr monitoring; susceptability to seizurigenic doses of cocaine and other stimulant agents, various measures of cognitive function (learning, memory, motivation, arousal, etc.) and rats' sensitivity to various classes of behaviorally active drugs. Rats will be tested in adulthood, after exposure prior to fertilization (gametes) and during in utero development. Treatment of neonates with cocaine and drugs known to attenuate or block opiate withdrawal in rat and/or humans will be used to determine if cocaine-exposed neonates shown morbidity or mortality as a result of residual cocaine of if toxicity and/or a withdrawal syndrome is treatable during the neonatal period. Since no such data currently exist in the literature, we expect to contribute to a nonexistent database with preliminary studies over the first 1-2 years, to establish appropriate dosing schedules for subsequent functional teratology and mechanistic experiments.
