Nicotine is the primary psychoactive component of tobacco smoke. Prenatal nicotine exposure may adversely impact fetal brain development through both indirect and direct mechanisms. Potential indirect mechanisms include maternal and fetal undernutrition secondary to smoking-induced anorexia, hypoxia due to increased carboxyhemoglobin and vasoconstriction, placental hypertrophy and reduced transplacental transport of nutrients169. Preclinical studies in rodents and primates have demonstrated the direct effects of fetal nicotine exposure on brain and body growth parameters and have shown that nicotine is a neuro-teratogen that targets several neurochemical systems, particularly NE170. Nicotine binds to nicotinic acetylcholine receptors (nAChRs) which become detectable during the embryonic development shortly before neurulation171. Acetylcholine (ACh) plays a crucial role in brain development and maturation, initially promoting cell division and subsequently promoting a switch from cell replication to differentiation. Stimulation of nAChRs by nicotine during gestation disrupts brain development, by altering these trophic effects of Ach170, 172. These neuro-developmental effects appear to be highly selective for particular brain regions172. Preclinical studies have also demonstrated changes in other monoamine systems following prenatal nicotine exposure. Dopamine synthesis and turnover is decreased in
