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Effect of cocaine in early gestation on striatal dopamine and neurotrophic activity
D E Weese-Mayer1, J M Silvestri, D Lin
1Department of Pediatrics, Rush Medical College, Rush University, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612.
Insights
Prenatal cocaine exposure in rabbits impairs brain development by reducing dopamine levels. This may stem from decreased striatal trophic activity, impacting neuronal growth.
Area of Science:
- Neuroscience
- Developmental Biology
- Pharmacology
Background:
- Prenatal exposure to cocaine, a dopamine agonist, is linked to adverse infant developmental outcomes.
- The precise mechanisms underlying these developmental deficits, particularly the role of neurotrophic factors, remain incompletely understood.
Purpose of the Study:
- To investigate the impact of prenatal cocaine exposure on striatal dopamine levels and neurotrophic activity in developing rabbit pups.
- To explore the potential role of reduced striatal trophic activity in mediating cocaine-induced neurodevelopmental impairments.
Main Methods:
- New Zealand White rabbit pups were exposed to cocaine (30 mg/kg/d) or a control (sterile H2O) during early gestation (days 7-15).
- Striatal dopamine and 3,4-dihydroxyphenyl acetic acid levels were measured in pups at 4-6 days old.
- Mesencephalic neuron cultures were incubated with striatal extracts from exposed and control pups to assess trophic activity via neuron-specific enolase immunoreactivity.
Main Results:
- Cocaine exposure significantly reduced striatal dopamine by 46% and 3,4-dihydroxyphenyl acetic acid by 49%.
- Striatal extracts from cocaine-exposed pups showed a 61% reduction in their ability to support neuron growth in mesencephalic cultures.
Conclusions:
- Prenatal cocaine exposure leads to significant reductions in striatal dopamine levels in early postnatal life.
- The findings suggest that cocaine-induced decreases in striatal trophic activity may contribute to the observed neurodevelopmental deficits.
Abstract:
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.