Apr. 23, 2004 DURHAM, N.C. -- Prenatal exposure to nicotine inflicts lasting damage that might leave the brain vulnerable to further injury and addiction upon later use of the drug, according to animal research conducted by Duke University Medical Center pharmacologists. The team found in rat studies that exposure to nicotine in fetal development alters the brain structures and brain cell activity in regions critical to learning, memory and reward.
In turn, those changes influence nicotine's effects on the brain during adolescence, a time when many smokers first take up the habit, the team found. The study in rats might provide a biological explanation for the high incidence of smoking among teens whose mothers smoked during pregnancy, the researchers said.
"Teens whose mothers smoked during pregnancy can show signs of nicotine dependence and withdrawal after just a handful of cigarettes," said Theodore Slotkin, Ph.D., professor of pharmacology, psychiatry and neurobiology at Duke. "Our study suggests a biological mechanism to explain that."
A pair of papers describing the findings, now available online, is set to appear in forthcoming issues of Neuropsychopharmacology. Philip Morris USA supported the research. The researchers have no financial ties to Philip Morris.
While maternal smoking rates have dropped in recent years, approximately 25 percent of individuals in the U.S. have mothers who smoked during pregnancy, Slotkin said. Epidemiological studies by other researchers have shown that such maternal smoking leaves children prone to smoke as adolescents, regardless of whether the parental smoking continues during childhood. That research was performed by researchers including Denise Kandel, Ph.D., of Columbia University, Marie Cornelius, Ph.D., of the University of Pittsburgh and Raymond Niaura, Ph.D., of Brown University.
"The best of these studies rule out socioeconomic and other factors and point toward something special about exposure to nicotine during the prenatal period," Slotkin said.
In search of a biological explanation for the pattern, the Duke team administered nicotine or placebo to pregnant rats. The offspring then received a secondary exposure to the drug or placebo during adolescence via implanted osmotic minipumps designed to produce blood nicotine concentrations typical of smokers.
The rats exposed to nicotine before birth suffered loss of brain cells and a decline in brain activity that persisted throughout adolescence and into adulthood, the team found.
When given doses of nicotine for a two-week period as adolescents, the earlier exposed rats showed a weaker brain response in circuits using acetylcholine -- a natural chemical messenger that plays a critical role in learning and memory -- as compared to rats that did not experience the prenatal exposure. Nicotine's activity in the brain stems from its ability to mimic acetylcholine. The earlier exposure also worsened the decline in brain activity during nicotine withdrawal and led to an increase in the amount of brain cell injury induced by the drug, they reported.
"The current study suggests that the lasting neurotoxic effects of prenatal exposure to nicotine from maternal smoking during pregnancy may worsen the long-term consequences of adolescent smoking -- effects that may increase the likelihood that an individual will take up and keep smoking," Slotkin said.
Specifically, the team explained, the reduced response of acetylcholine systems in the adolescent brain following prenatal exposure might lead teens to self-administer nicotine in an attempt to replace the brain's functional loss. Furthermore, that deficient brain response might drive higher cigarette consumption.
Collaborators on the studies include Yael Abreu-Villaca, Ph.D., Frederic Seidler, Ph.D., Charlotte Tate and Mandy Cousins, all of Duke.
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