An assessment of the long-term developmental and behavioral teratogenicity of prenatal nicotine exposure

Abstract

Maternal tobacco use during pregnancy adversely affects prenatal and postnatal growth and increases the risk of developmental and behavioral deficits in children and adolescents. In the present study, the effects of prenatal nicotine exposure (infused at 6mg/kg/day) and maternal withdraw during neonatal development, was examined in Sprague-Dawley rats on an array of behavioral tasks during different stages of ontogenesis. Offspring of both genders were monitored for exploratory, locomotor, and novelty-seeking activity, anxiety, and learning and memory in an active-avoidance task. Nicotine-exposed animals showed growth retardation, hyperactivity, and poor adaptation in a new environment, increased level of anxiety during the early adolescent period, and robust cognitive deficits in early adulthood. In addition, the deficits were generally more severe in the female nicotine-exposed offspring. Cross-fostering also revealed that while maternal behavior and nicotine withdraw did not affect postnatal somatic growth retardation or cognitive ability of the offspring; measures of exploration and adaptation in a new environment were impacted during the post-weanling and early adolescence period. Nicotine-exposed offspring, and the saline-treated offspring cross-fostered to nicotine-exposed mothers, showed higher measures of anxiety in the elevated plus-maze and decreased novelty-seeking behavior on the hole-board apparatus. These studies demonstrated that prenatal nicotine exposure produced significant long-term developmental and behavioral teratogenic effects. The study design provides a model system for studying the mechanism(s) responsible for the decline in central nervous system function following prenatal nicotine exposure, as well as that of other neurological and behavioral teratogens during pregnancy.