Effect of cocaine in early gestation on striatal dopamine and neurotrophic activity.
Prenatal exposure to the dopamine (DA) agonist cocaine, even if limited to early gestation, is associated with impaired developmental outcome in the human infant. We investigated the possible role of neurotrophic factors in this process by evaluating 4- to 6-d-old New Zealand White rabbit pups (n = 14) born to cocaine-exposed does (30 mg/kg/d s.c. from days 7 to 15 of a 32-d gestation) and control does (sterile H2O). Cocaine exposure reduced striatal dopamine by 46% (t = 2.31; p < 0.05) and striatal 3,4-dihydroxyphenyl acetic acid by 49% (t = 2.44; p < 0.05). The number of neuron-specific enolase immunoreactive neurons in mesencephalic cultures incubated with striatal extracts from pups exposed to cocaine was reduced by 61% relative to the effect of striatal extracts from control pups (t = 4.84; p < 0.01). The present results suggest that the reduction in striatal dopamine observed may result from a cocaine-induced decrease in striatal trophic activity.
Weese-Mayer
D E
DE
Department of Pediatrics, Rush Medical College, Rush University, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612.
Silvestri
J M
JM
Lin
D
D
Buhrfiend
C M
CM
Lo
E S
ES
Carvey
P M
PM
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000014:Abnormalities, Drug-Induced / Q000196:embryology / Q000209:etiology* / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D002531:Cerebellum / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D003042:Cocaine / Q000494:pharmacology / Q000633:toxicity*; D003342:Corpus Striatum / Q000002:abnormalities / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism / Q000473:pathology; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D011247:Pregnancy; D011817:Rabbits
D015102:3,4-Dihydroxyphenylacetic Acid; D003042:Cocaine; D004298:Dopamine