Current animal models of nicotine addiction may not accurately reflect the biophysical changes that occur inthe dopaminergic system and that may be associated with tobacco addiction. This proposal is designed toaddress a specific concern in regards to studies of tobacco addiction: the effects of multiple smokeconstituents on the dopaminergic system (which is primarily involved in tobacco addiction). Current modelsof tobacco addiction focus solely on chronic nicotine administration and have not included other bioactivecomponents of cigarette smoke, such as monoamine oxidase B (MAO-B) inhibitors, that are potentmodulators of dopaminergic function. This is a potentially serious oversight since MAO-B inhibitors arepresent in significant amounts in cigarette smoke, along with nicotine. The research proposed in thisapplication is designed to examine the effects of chronic nicotine administration in combination with chronicMAO-B inhibition in the mouse brain.
Specific aim 1 is designed to study the extent to which chronicexposure to nicotine and an MAO-B inhibitor affects the dopaminergic system in young adult animals (bymeasuring dopamine & metabolite levels, MAO-B activity, tyrosine hydroxylase protein and mRNAexpression, and dopamine transporter expression) and nicotinic acetylcholine receptor(nAChR) expression.
Specific aim 2 studies are designed to examine the extent to which changes that occur in the neuronaldopaminergic and nAChR systems effects function of these systems. Thus, specific aim 2 studies willexamine the effects of chronic nicotine and MAO-B inhibitor exposure, singly and in combination, ondopamine uptake and nicotine-evoked dopamine release. This proposal is designed to establish a more physiologically accurate model for tobacco addiction.Relevance: The effects of tobacco smoking on public health are well known. Unfortunately, currentmethods to treat tobacco addiction are not always successful. This project will investigate a model forsmoking that may more accurately reflect the changes in the brain seen with tobacco addiction and mayprovide an improved research model for smoking cessation.
