Prenatal cocaine and cell development in rat brain regions: effects on ornithine decarboxylase and macromolecules.
Prenatal cocaine exposure has been shown to cause neurobehavioral abnormalities. To determine whether effects on basic patterns of cell development underlie these functional deficits, we examined the aftermath of acute and chronic cocaine exposure on ontogenetic patterns of ornithine decarboxylase (ODC), a key regulator of cell replication/differentiation, DNA synthesis as monitored by [3H]thymidine incorporation, and markers of cell number (DNA content) and cell size (protein/DNA ratio). Administration of 30 mg/kg SC of cocaine to pregnant rats on gestational day 20 resulted in acute increases of ODC throughout the brain. When the same dose of cocaine was given daily from gestational days 8 through 20, ODC elevations persisted into the neonatal period but disappeared by the middle of the first postnatal week. Although this treatment regimen retarded maternal weight gain, there was little or no effect on pup body or brain region weights. Similarly, minor changes in DNA synthesis were seen in two brain regions (forebrain, cerebellum), but DNA content was largely unaffected. Postnatal cell growth was significantly reduced in the forebrain, as evidenced by deficits in protein/DNA but, again, the magnitude of effect was quite small. Raising the daily dose of cocaine to 100 mg/kg resulted in significant maternal mortality and fetal resorptions in surviving dams. Shortening the treatment regimen to a 3-day period (gestational days 18 through 20) eliminated the effects on maternal weight gain and on postnatal pup brain region ODC.(ABSTRACT TRUNCATED AT 250 WORDS)
Seidler
F J
FJ
Department of Pharmacology, Duke University Medical Center, Durham, NC 27710.
Slotkin
T A
TA
D000375:Aging / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D001933:Brain Stem / Q000201:enzymology; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism*; D004334:Drug Administration Schedule; D005314:Embryonic and Fetal Development; D005260:Female; D005327:Fetal Resorption; D005865:Gestational Age; D008431:Maternal-Fetal Exchange; D008636:Mesencephalon / Q000201:enzymology; D009929:Organ Size / Q000187:drug effects; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D016548:Prosencephalon / Q000201:enzymology; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D011506:Proteins; D004247:DNA; D009955:Ornithine Decarboxylase; D003042:Cocaine