Fetal nicotine or cocaine exposure: which one is worse?
Despite extensive adverse publicity, tobacco use continues in approximately 25% of all pregnancies in the United States, overshadowing illicit drugs of abuse, including cocaine. The societal cost of maternal smoking is seen most readily in underweight newborns, in high rates of perinatal morbidity, mortality and Sudden Infant Death Syndrome and in persistent deficits in learning and behavior. We have designed animal models of nicotine exposure to prove that nicotine itself is a neuroteratogen, thus providing a causative link between tobacco exposure and adverse perinatal outcomes. In particular, nicotine infusion paradigms that, like the transdermal patch used in man, produce drug exposure without the confounds of other components of tobacco or of episodic hypoxic-ischemic insult, have enabled a mechanistic dissection of the role played by nicotine in fetal brain damage. Nicotine targets specific neurotransmitter receptors in the fetal brain, eliciting abnormalities of cell proliferation and differentiation, leading to shortfalls in the number of cells and eventually to altered synaptic activity. Because of the close regulatory association of cholinergic and catecholaminergic systems, adverse effects of nicotine involve multiple transmitter pathways and influence not only the immediate developmental events in fetal brain, but also the eventual programming of synaptic competence. Accordingly, defects may appear after a prolonged period of apparent normality, leading to cognitive and learning defects that appear in childhood or adolescence. Comparable alterations occur in peripheral autonomic pathways, leading to increased susceptibility to hypoxia-induced brain damage, perinatal mortality and Sudden Infant Death. Identifying the receptor-driven mechanisms that underlie the neurobehavioral damage caused by fetal nicotine exposure provides a rational basis for decisions about nicotine substitution therapy for smoking cessation in pregnancy. In contrast to the effects of nicotine, animal models of crack cocaine use in pregnancy indicate a more restricted spectrum of effects, a reflection of differences both in pharmacokinetics and pharmacodynamics of the two drugs. Notably, although cocaine, like nicotine, also targets cell replication, its effects are short-lived, permitting recovery to occur in between doses, so that the eventual consequences are much less severe. To some extent, the effects of cocaine on brain development resemble those of nicotine because the two share cardiovascular actions (vasoconstriction) that, under some circumstances, elicit fetal hypoxia-ischemia. In light of the fact that nearly all crack cocaine users smoke cigarettes, the identification of specific developmental effects of cocaine may prove difficult to detect. Although scientists and the public continue to pay far more attention to fetal cocaine effects than to those of nicotine or tobacco use, a change of focus to concentrate on tobacco could have a disproportionately larger impact on human health.
Slotkin
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TA
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina, USA.
D003042:Cocaine / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D005260:Female; D005333:Fetus / Q000187:drug effects*; D005731:Ganglionic Stimulants / Q000494:pharmacology*; D006801:Humans; D007226:Infant Mortality; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000209:etiology; D018377:Neurotransmitter Agents / Q000502:physiology; D009538:Nicotine / Q000494:pharmacology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011978:Receptors, Nicotinic / Q000187:drug effects; D012307:Risk Factors; D012907:Smoking; D019966:Substance-Related Disorders; D013398:Sudden Infant Death / Q000209:etiology
D018765:Dopamine Uptake Inhibitors; D005731:Ganglionic Stimulants; D018377:Neurotransmitter Agents; D011978:Receptors, Nicotinic; D009538:Nicotine; D003042:Cocaine