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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center (P50)
Project #
3P50CA084718-01S2
Application #
6366922
Study Section
Special Emphasis Panel (ZCA1)
Project Start
1999-09-30
Project End
2000-09-29
Budget Start
Budget End
Support Year
1
Fiscal Year
2000
Total Cost
$245,224
Indirect Cost
Name
Georgetown University
Department
Type
DUNS #
049515844
City
Washington
State
DC
Country
United States
Zip Code
20057
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