Prenatal cocaine exposure alters postnatal ornithine decarboxylase activity in rabbit brain.
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)
Gingras
J L
JL
Department of Pediatrics, Duke University Medical Center, Durham, North Carolina 27710.
Weese-Mayer
D E
DE
Dalley
L B
LB
Klemka-Walden
L M
LM
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D003042:Cocaine / Q000633:toxicity*; D005260:Female; D005333:Fetus / Q000187:drug effects*; D009748:Nutrition Disorders / Q000378:metabolism; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011817:Rabbits
D009955:Ornithine Decarboxylase; D003042:Cocaine