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Hyperactive nicotine receptors

Institution: California Institute of Technology
Investigator(s): Henry Lester, Ph.D.
Award Cycle: 2000 (Cycle 9) Grant #: 9RT-0182 Award: $1,138,225
Subject Area: Nicotine Dependence
Award Type: Research Project Awards

Initial Award Abstract
In the first step in the biology of nicotine addiction, molecules of nicotine touch “receptor molecules” on cells in the brain. The receptors start a chain of chemical and electrical events that we do not yet understand. If we understood them, perhaps we could avoid or cure nicotine addiction. We wish to use genetic engineering to address this problem. We shall study mice whose nicotine receptors are much more sensitive than usual. Will these mice be addicted to nicotine before ever experiencing nicotine? Will these mice never become addicted to nicotine? Will their brain cells act normally or differently? We will study the behavior of these mice and we will also measure the electrical properties of their brain cells. We think that this procedure will provide new insights into the events that lead to nicotine addiction.

Point mutant mice with hypersensitive alpha4 nicotinic receptors show dopaminergic deficits and increased anxiety
Periodical: Proceedings of the National Academy of Sciences of the United States of America Index Medicus:
Authors: Labarca C, Schwarz J, Deshpande P, et al ART
Yr: 98 Vol: Nbr: Abs: Pg: 2786-2791

Increased sensitivity to agonist-induced seizures, straub tail, and hippocampal theta rhythm in knock-in mice carrying hypersensitive alpha 4 nivotinic receptors.
Periodical: Journal of Neuroscience Index Medicus:
Authors: Fonck C, Nashmi R, Deshpande P, Damaj M, Riedel A, Schwarz J, Collins A, ART
Yr: 2003 Vol: 23 Nbr: 7 Abs: Pg: 2582-2590

Alpha4Beta2* nicotinic acetylcholine receptors modulate the effects of ethanol and nicotine on the acoustic startle response targets for both nicotine and ethanol.
Periodical: Alcoholism: Clinical and Experimental Research Index Medicus:
Authors: Owens JC, Balogh SA, McClure-Begley TD, Butt CM, Mabarca C, Lester HA, ART
Yr: 2003 Vol: 27 Nbr: Abs: Pg: 1867-75

Assembly of alpha4beta2 nicotinic acetylcholine receptors assessed with functional fluorescently labeled subunits: Effects of localization, trafficking, and nicotine-induced upregulation in clonal mammalian cells and in cultured midbrain neurons.
Periodical: Journal of Neuroscience Index Medicus:
Authors: Nashmi R, Dickinson ME, McKinney S, Jareb M, Labarca C, Fraser SE, Lester HA ART
Yr: 2003 Vol: 23 Nbr: Abs: Pg: 11554-11567