Ornithine decarboxylase, a modulator of tissue growth during fetal and neonatal mammalian development, serves as a sensitive marker enzyme for perturbations in neural development. To test the hypothesis that cocaine is a central nervous system neurodevelopmental teratogen through mechanisms involving direct cellular injury, we measured ornithine decarboxylase activity in brain sections of 4- to 6-day-old rabbit pups which were prenatally cocaine exposed and in pair-fed and free-fed controls. Rabbit does were implanted with the osmotic minipump prior to Gestational Day 10 and cocaine and/or sterile water was delivered between Gestational Days 10 and 32. The flow rate in the cocaine group was calculated to provide a daily cocaine dose of 30 mg/kg/day. Pups were sacrificed, brains were dissected into the cortex, pons, and medulla, and ornithine decarboxylase activity was measured. When compared to the pair-fed group, prenatal cocaine exposure significantly decreased ornithine decarboxylase activity in the cortex (0.531 ± 0.070 nmol/g/h SEM vs 0.913 ± 0.201 nmol/g/h SEM; cocaine vs pair fed, respectively; P ≤ 0.05) and in the pons (0.533 ± 0.036 nmol/g/h SEM vs 0.728 ± 0.075 nmol/g/h SEM, cocaine vs pair fed, respectively; P ≤ 0.05) but not in the medulla (0.374 ± 0.040 nmol/g/h SEM vs 0.392 ± 0.045 nmol/g/h SEM, cocaine vs pair fed, respectively; P > 0.05). Although there were no statistically significant differences in ornithine decarboxylase activity between the cocaine-exposed group and the free-fed group in any brain region, all regions showed a relative decrease in ornithine decarboxylase activity with prenatal cocaine exposure. These data support the concept that prenatal cocaine exposure and malnutrition play a role in the adverse central nervous system outcomes associated with prenatal cocaine exposure.
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism