PRENATAL NICOTINE EXPOSURE: HOW DOES IT RELATE TO DEVELOPMENTAL VULNERABILITIES?
Nicolette Borek, Ph.D.
National Institute on Drug Abuse
Allison Chausmer, Ph.D.
National Institute on Drug Abuse
Impressive advances have been made in examining relationships between prenatal nicotine exposure and developmental vulnerabilities among the exposed offspring. For example, a strong association has been reported between maternal smoking during pregnancy and disruptive behavior disorders in childhood. This symposium: (1) examines associations between prenatal nicotine exposure and neurobiological and behavioral vulnerabilities in the developmental period from birth into adolescence, (2) considers possible mechanisms underlying these relationships, and (3) examines implications of the research for clinical practice. Using focused presentations and interactions between the speakers and the attendees, the symposium addresses multiple developmental outcome areas, reflects findings from clinical and preclinical studies, and includes neurobiological, behavioral, and neuroimaging data. This symposium is intended for individuals with clinical and/or research interest in the effects of prenatal risk factors on the development of clinical disorders.
Neuroimaging Evidence of Altered Medial Temporal Lobe Function in Adolescent Tobacco Smokers With Prenatal Exposure to Maternal Smoking
Leslie K. Jacobsen, M.D.
Prenatal exposure to active maternal tobacco smoking elevates risk of cognitive and auditory processing deficits, and of smoking in offspring. Recent preclinical work has demonstrated a gender-specific pattern of reduction in cortical cholinergic markers following prenatal, adolescent, or combined prenatal and adolescent exposure to nicotine, the primary psychoactive component of tobacco smoke. Given the importance of cortical cholinergic neurotransmission to attentional function, we examined auditory and visual selective and divided attention in 181 male and female adolescent smokers and nonsmokers with and without prenatal exposure to maternal smoking. Groups did not differ in age, educational attainment, symptoms of inattention, or years of parent education. A subset of 63 subjects also underwent functional magnetic resonance imaging while performing an auditory and visual selective and divided attention task. Among females, exposure to tobacco smoke during prenatal or adolescent development was associated with reductions in auditory and visual attention performance accuracy that were greatest in female smokers with prenatal exposure (combined exposure). Among males, combined exposure was associated with marked deficits in auditory attention, suggesting greater vulnerability of neurocircuitry supporting auditory attention to insult stemming from developmental exposure to tobacco smoke in males. Activation of brain regions that support auditory attention was greater in adolescents with prenatal or adolescent exposure to tobacco smoke relative to adolescents with neither prenatal nor adolescent exposure to tobacco smoke. These findings extend prior preclinical work and suggest that, in humans, prenatal and adolescent exposure to nicotine exerts gender-specific deleterious effects on auditory and visual attention, with concomitant alterations in the efficiency of neurocircuitry supporting auditory attention.
Prenatal Nicotine Exposure Induces Sex-Dependent Changes in Dopamine Pathways in Adolescent Brain
Frances Leslie, Ph.D.
Central dopamine systems serve numerous integrative neural functions and critically regulate action, emotion, motivation, and cognition. Dysregulation of these systems has been implicated in numerous disease states, particularly those in which there are cognitive, emotional, and/or motor deficits. Numerous clinical studies have shown that smoking during pregnancy can lead to long-standing neurobehavioral deficits in the offspring, many of which may result from central dopamine dysfunction, including attention deficit hyperactivity disorder, conduct disorder, cognitive deficits, and substance abuse. Using rats as a model, we have demonstrated that nicotine, the major psychoactive component of tobacco, targets dopamine systems in fetal brain. Chronic prenatal nicotine (PN) exposure, via an osmotic minipump, produces long-lasting changes in the properties of central dopamine neurons. In particular, sex-dependent changes in regional levels of dopamine and dopamine transporter (DAT) are observed in adolescent brains. Cocaine, which mediates many of its effects through blockade of DAT, also exhibits substantial behavioral differences in PN-treated rats, including alterations in drug self-administration, locomotion, and stereotypy. These findings suggest that not only smoking, but also the use of nicotine patch during pregnancy may substantially disrupt brain development. Thus, the safety of nicotine replacement therapy as a therapeutic regimen during pregnancy and adolescence must be evaluated more thoroughly.