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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.