To elucidate mechanisms of nicotine-induced neurotoxicity in the context of central nervous system development. Additionally, to determine whether critical periods exist for these mechanisms. In animal studies, prenatal nicotine exposure results in CNS cell loss, altered nicotinic cholinergic receptor expression, perturbed synaptic function, and elevation of genes putatively involved in apoptosis.
Prenatal exposure is capable of influencing later events in differentiation and survival of neurons.
It is unclear whether this period of vulnerability extends into later development, up to adolescence, when many synaptic connections are still being forged and others deleted. Overall, this research will impact on regulatory issues involving tobacco and nicotine and, hopefully, raise public awareness about these commonly used products. Prenatal exposure is achieved via implantation of an osmotic minipump in dams on gestational day 4, with exposure continuing until gestational day 21. Adolescent exposure, also via minipump implantation, extends from postnatal day 30 to 47. Several parameters are measured both during and up to several weeks following the exposure period in a variety of brain regions.