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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA004979-03
Application #
2117354
Study Section
Drug Abuse Biomedical Research Review Committee (DABR)
Project Start
1988-08-01
Project End
1994-11-30
Budget Start
1992-05-01
Budget End
1994-11-30
Support Year
3
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Pharmacology
Type
Schools of Medicine
DUNS #
168559177
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Bollweg, G L; Sparber, S B (1999) Voltage associated with spontaneous embryonic motility in the developing chicken: an automated characterization during mid-late embryogenesis. Dev Psychobiol 34:5-19
Schrott, L M; Getty, M E; Wacnik, P W et al. (1998) Open-field and LPS-induced sickness behavior in young chickens: effects of embryonic cocaine and/or ritanserin. Pharmacol Biochem Behav 61:9-17
Bollweg, G; Wei, Y X; Sparber, S B (1998) Behavioral and neuroendocrine assessment of ritanserin exposure in the developing chicken: lack of toxicity at effective doses. Pharmacol Biochem Behav 60:175-81
Zhang, X; Schrott, L M; Sparber, S B (1998) Evidence for a serotonin-mediated effect of cocaine causing vasoconstriction and herniated umbilici in chicken embryos. Pharmacol Biochem Behav 59:585-93
Bollweg, G; Sparber, S B (1998) Relationships between midembryonic 5-HT2 agonist and/or antagonist exposure and detour learning by chickens. Pharmacol Biochem Behav 60:47-53
Bordone, L; Schrott, L M; Sparber, S B (1997) Ontogeny of glucocorticoid receptors in the hyperstriatum-hippocampus-parahippocampal area and optic tectum of the embryonic chicken (Gallus domesticus) brain. J Neuroendocrinol 9:753-61
Bollweg, G; Sparber, S (1996) Ritanserin blocks DOI-altered embryonic motility and posthatch learning in the developing chicken. Pharmacol Biochem Behav 55:397-403
Bollweg, G; Balaban, C; Cox, H J et al. (1995) Potential efficacy and toxicity of GM1 ganglioside against trimethyltin-induced brain lesions in rats: comparison with protracted food restriction. Neurotoxicology 16:239-55
Sparber, S B (1991) Measurement of drug-induced physical and behavioral delays and abnormalities in animal studies: a general framework. NIDA Res Monogr 114:148-64
Livezey, G T; Sparber, S B (1990) Hyperthermia sensitizes rats to cocaine's proconvulsive effects and unmasks EEG evidence of kindling after chronic cocaine. Pharmacol Biochem Behav 37:761-7