The mesolimbic system has been implicated in the addictive properties of most drugs of abuse and dependence including cocaine, heroin, amphetamines and nicotine from tobacco. Nicotine affects the dopaminergic system in multiple ways including increasing both the firing rate and bursting activity of dopaminergic cells and by enhancing synthesis, metabolism and release of dopamine. In these studies we propose to examine, using an animal model, the acute and chronic effects of nicotine of dopaminergic function (dopamine release and dopamine uptake) at various developmental ages. The relationship The relationship between the nicotine-induced change in nicotine acetylcholine receptor (nAChR) numbers following chronic prenatal nicotine and the number of dopamine transports will also be assessed. Finally, the identify of the nAChR involved in the dopaminergic regulation will be determined by labeling the receptors with [125I]epibatidine, a high affinity radioligand for a variety of nAChRs, and immunoprecipitation of the receptors with subunit-specific antibodies. To determine the identify of these nAChRs involved in regulating dopaminergic function may lead us to a better understanding of nicotine's effects in brain and in addictive properties during various developmental stages. This knowledge will also help in the development of specific therapeutics, as well as in assessing the validity of using nicotine as a therapeutic agent in developmental disorders or during pregnancy as an aid to quit smoking.
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