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Hyperactive nicotine receptors

Institution: California Institute of Technology
Investigator(s): Henry Lester, Ph.D.
Award Cycle: 1997 (Cycle 6) Grant #: 6RT-0044 Award: $486,158
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 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 breed 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.
Publications

From ab initio quantum mechanics to molecular neurobiology: A cation- binding site in the nicotinic receptor
Periodical: Proceedings of the National Academy of Sciences of the United States of America Index Medicus:
Authors: Zhong W, Gallivan JP, Zhang Y, Li L, Lester HA, Dougherty DA ART
Yr: 1998 Vol: 95 Nbr: Abs: Pg: 12088-12095

Point mutant mice with hypersensitive a4 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: 2001 Vol: 98 Nbr: Abs: Pg: 2786-2791