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Nicotinic receptors in nicotine addiction

Institution: California Institute of Technology
Investigator(s): Henry Lester, Ph.D.
Award Cycle: 2008 (Cycle 17) Grant #: 17RT-0127 Award: $634,743
Subject Area: Nicotine Dependence
Award Type: Research Project Awards
Abstracts

Initial Award Abstract
In the first step in the biology of nicotine addiction, molecules of nicotine touch “receptor molecules” on nerve cells in the brain. There are several types of nicotine receptors. We understand that the nicotine receptors electrically excite their nerve cells. However, chronic exposure to nicotine (for instance during tobacco smoking) starts a poorly understood chain of chemical events that apparently comprise the cellular and circuit basis of addiction. If we understood these events, perhaps we could avoid or cure nicotine addiction. We wish to use genetic engineering to address this problem.

We will construct and study mice with fluorescent nicotine receptors, and then we will determine the location and numbers of these receptors. These strains will become a valuable tool to test the hypothesis that chronic exposure to nicotine increases the levels and function of some receptors. We think that these measurements will provide new insights into the events that lead to nicotine addiction.
Publications

In Vivo Activation of Midbrain Dopamine Neurons via Sensitized, High-Affinity a6* Nicotinic Acetycholine Receptors.
Periodical: Neuron Index Medicus:
Authors: Drenan, RM, Grady, SR. Whiteaker, P, McClure-Begley, T, McKinney, SJ, Miwa, JM, Bupp, S, ART
Yr: 2008 Vol: 60 Nbr: 1 Abs: Pg: 123-36

Chronic nicotine selectively enhances a4B2 nicotinic acetycholine receptors in the nigrostriatal dopamine pathway
Periodical: Journal of Neuroscience Index Medicus:
Authors: Xiao, C, Nashmi, R, McKinney, S, Cai, H, McIntosh, JM, Lester, HA ART
Yr: 2009 Vol: Nbr: Abs: Pg: