Affiliations: College of Pharmacy, Department of Pharmaceutical
Sciences, University of Kentucky, Lexington, KY, USA
Note: [] Correspondence: James R. Pauly, Ph.D., Department of
Pharmaceutical Sciences, College of Pharmacy, Spinal Cord and Brain Injury
Research Center, University of Kentucky, 789 S. Limestone Street, Lexington, KY
40536-0596, USA. Tel.: +1 859 323 8164; Fax: +1 859 257 7564; E-mail: jpauly@uky.edu
Abstract: Tobacco use during pregnancy continues to be a major problem with
more than 16% of women in the United States continuing to smoke while
pregnant. Tobacco smoke is known to contain more than 4,000 different
chemicals, and while many of these compounds have the potential to interfere
with proper neurodevelopment, there is direct evidence that nicotine, the major
psychoactive substance present in tobacco, acts as a neuroteratogen. Nicotine
activates, and subsequently desensitizes, neuronal nicotinic acetylcholine
receptor subtypes (AChRs), which are expressed in the developing central
nervous system (CNS) prior to the in-growth of cholinergic neurons. Nicotinic
AChRs are present by the first trimester of development in both humans and
rodents, and activation of these receptors by acetylcholine is thought to play
a critical role in CNS development. The purpose of the current review is to
provide an overview of the role that nicotinic AChRs play in the developing CNS
and to describe the effects of nicotine exposure during early development on
neuronal cell biology, nicotinic AChR expression and neurotransmitter system
(e.g., dopamine, norepinephrine, serotonin) function. In particular,
differences that occur as a result of the timing and duration of nicotine
exposure will be discussed. Emphasis will be placed on preclinical studies
examining particular periods of time which correspond to periods of prenatal
development in humans (i.e., first, second and third trimesters). Finally, the
effects of early nicotine exposure on neurobehavioral development as it
pertains to specific disorders, i.e., attention deficit hyperactivity disorder
(ADHD), depression and addiction, will be discussed.
