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Prenatal cocaine exposure alters postnatal ornithine decarboxylase activity in rabbit brain
J L Gingras1, D E Weese-Mayer, L B Dalley
1Department of Pediatrics, Duke University Medical Center, Durham, North Carolina 27710.
Abstract:
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 < or = 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 < or = 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Prenatal cocaine exposure significantly reduced ornithine decarboxylase activity in the cortex and pons of newborn rabbits, suggesting cocaine may harm neural development. This enzyme is a key marker for tissue growth and neural development.
Area of Science:
- Neuroscience
- Developmental Biology
- Pharmacology
Background:
- Ornithine decarboxylase (ODC) is crucial for mammalian tissue growth during development.
- ODC activity serves as a sensitive indicator of neural development disruptions.
- Cocaine's potential as a neurodevelopmental teratogen warrants investigation into its cellular injury mechanisms.
Purpose of the Study:
- To test if cocaine acts as a central nervous system neurodevelopmental teratogen.
- To investigate if cocaine causes neural developmental harm through direct cellular injury.
- To measure ornithine decarboxylase activity in rabbit pups prenatally exposed to cocaine.
Main Methods:
- Rabbit does received osmotic minipumps delivering 30 mg/kg/day of cocaine or sterile water from Gestational Day 10 to 32.
- Ornithine decarboxylase activity was measured in brain sections (cortex, pons, medulla) of 4- to 6-day-old pups.
- Activity was compared between cocaine-exposed, pair-fed, and free-fed control groups.
Main Results:
- Prenatal cocaine exposure significantly decreased ODC activity in the cortex and pons compared to pair-fed controls (P < 0.05).
- No significant difference in ODC activity was observed in the medulla between cocaine-exposed and pair-fed groups (P > 0.05).
- While not statistically significant, all brain regions showed a relative decrease in ODC activity following prenatal cocaine exposure compared to free-fed controls.
Conclusions:
- Prenatal cocaine exposure demonstrably alters ODC activity in specific brain regions of developing rabbits.
- These findings support the hypothesis that cocaine may act as a neurodevelopmental teratogen, potentially via cellular injury mechanisms.
- ODC activity is a valuable biomarker for assessing the impact of prenatal drug exposure on neural development.