Prenatal cocaine exposure.
Cocaine abuse is a significant problem not only in the general population but also among pregnant women. Since cocaine readily crosses the placenta and is metabolized slowly in fetuses, they can be exposed to significant levels of cocaine for long periods. In humans the most common consequences of cocaine abuse during pregnancy include premature birth, lower birth weight, respiratory distress, bowel infarctions, cerebral infarctions, reduced head circumference, and increased risk of seizures. Behaviorally these newborns show an increased degree of "tremulousness," crying and irritability, and are over-reactive to environmental stimuli. Within a month these behaviors have recovered dramatically, but not to normal levels. Thus while there are a number of abnormalities associated with cocaine-exposed neonates, they are not imminently debilitating or life-threatening. However, the long-term consequences of this prenatal cocaine exposure remain to be elucidated. We have examined a rat model for neurochemical, neuroanatomical and behavioral changes resulting from prenatal cocaine exposure. Since cocaine is known to act by blocking the inactivation of the neurotransmitters dopamine, serotonin and norepinephrine, our studies have focused on brain dopamine (DA) and serotonin (5-HT) pathways. In this model system we have found neurochemical changes that are present at birth and that return to normal as the rat ages--similar to the recovery observed in infants. However, there are other neurochemical, anatomical and behavioral changes that persist after birth which may provide insights into the long-term consequences. It is hoped that by understanding the changes occurring in this rat model we will be better prepared to devise pharmacological interventions to circumvent the secondary consequences of prenatal cocaine exposure. These consequences might include increased susceptibility to drug addiction, seizures, depression, schizophrenia, Parkinson's disease, etc.
Center for Neuropharmacology & Neuroscience, Albany Medical College, New York 12208, USA. kellerr@mail.amc.edu
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Keller
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Snyder-Keller
D000818:Animals; D003042:Cocaine / Q000493:pharmacokinetics / Q000633:toxicity*; D003342:Corpus Striatum / Q000187:drug effects; D004298:Dopamine / Q000502:physiology; D005260:Female; D005333:Fetus / Q000187:drug effects*; D006801:Humans; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects; D011247:Pregnancy; D051381:Rats; D012640:Seizures / Q000139:chemically induced; D012646:Self Administration; D012701:Serotonin / Q000502:physiology
D012701:Serotonin; D003042:Cocaine; D004298:Dopamine