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Transplacental cocaine exposure. 3: Mechanisms underlying altered brain development
A S Wilkins1, J J Marota, E Tabit
1Laboratory of Molecular and Developmental Neuroscience, Massachusetts General Hospital, Boston, USA.
Neurotoxicology and Teratology
|June 25, 1998
Summary
Transplacental cocaine exposure causes brain deficits in offspring. Alpha-adrenergic mechanisms, including maternal vasoconstriction, are unlikely to cause these developmental effects in mice.
Area of Science:
- Neuroscience
- Developmental Biology
- Pharmacology
Background:
- Transplacental cocaine exposure can lead to adverse neurodevelopmental outcomes in offspring.
- Cocaine-induced alpha-adrenergic-mediated uterine arterial vasoconstriction is a proposed mechanism for fetal brain alterations.
- Previous studies suggest cocaine exposure disrupts fetal brain growth, cytoarchitecture, and behavior.
Purpose of the Study:
- To investigate the role of alpha-adrenergic mechanisms in mediating the neurodevelopmental effects of transplacental cocaine exposure in a mouse model.
- To determine if maternal vasoconstriction contributes to cocaine's teratogenic effects on fetal brain development.
Main Methods:
- Pregnant Swiss Webster mice were administered cocaine hydrochloride (HCl) at various doses (10-40 mg/kg/day) from embryonic day 8 to 17.
- Some cocaine-treated dams received phentolamine, an alpha-adrenergic antagonist, prior to cocaine administration.
- Offspring were assessed for postnatal brain growth, and behavioral deficits using conditioning and blocking paradigms.
Main Results:
- Cocaine exposure did not alter maternal mean arterial blood pressure, suggesting lack of maternal vasoconstriction.
- Offspring from dams treated with cocaine and phentolamine showed similar transient postnatal growth retardation and behavioral deficits as those exposed to cocaine alone.
- Both cocaine-only and phentolamine-cocaine offspring exhibited persistent deficits in a blocking paradigm, indicating alpha-adrenergic pathways are not the primary mediators.
Conclusions:
- Maternal alpha-adrenergic mechanisms, including uterine vasoconstriction, are unlikely to be the primary mediators of transplacental cocaine's toxic effects on fetal brain development.
- Cocaine's adverse effects on offspring brain development and behavior occur independently of maternal alpha-adrenergic responses in this rodent model.
- Further research is needed to elucidate the precise mechanisms underlying cocaine's neuroteratogenic potential.