Neuronal nicotinic receptor trafficking in nicotine addictio

California Institute of Technology
Investigator(s): Raad  Nashmi , Ph.D. -
Award Cycle: 2001 (Cycle X) Grant #: 10FT-0174 Award: $71,664
Subject Area: Nicotine Dependence >
Award Type: Postdoctoral Fellowship Awards >


Initial Award Abstract
Nicotine addiction plays an important role in repetitive tobacco use. However, the exact mechanism of nicotine addiction is unknown. Specific subtypes of nicotinic acetylcholine receptors are activated by low concentrations of nicotine. Nicotinic receptors in the brain of smokers are exposed to nicotine for long durations. Prolonged application of nicotine is known to decrease the activity of nicotinic receptors. This study will examine whether the decrease in nicotinic receptor activity is associated with a change in localization of the receptors. Do the receptors get transported inside from the cell surface and therefore can no longer function? This will be studied using cultured cells. In addition, a mouse model will be used to examine changes in nicotinic receptor expression in specific brain regions. This will provide clues to which brain regions play an important role in 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: Proc Nat Acad Sci, U S A
  Authors: Labarca C, Schwarz J, Deshpande P, Schwarz S, Nowak M, Fonck C, Nashmi R, Kofuji P, et al.
  Yr: 2001 Vol: 98 Nbr: Abs: Pg:2786-2791
Increased sensitivity to agonist-induced seizures, straub tail, and hippocampal theta rhythm in knock-in mice carrying hypersensitive alpha4 nicotinic receptors.
Periodical:Journal of Neuroscience Index Medicus: J Neurosci
  Authors: Fonck C, Nashmi R, Deshpande P, Damaj M, Marks MJ, Riedel A, Schwarz J, Colllins AC, et al
  Yr: 2003 Vol: 23 Nbr: Abs: Pg:2582-2590
Knock-in mice carrying hypersensitive alpha4 nicotinic receptors: nicotine responses.
Periodical:Society for Neuroscience Abstracts Index Medicus: Soc Neurosci (Abs)
  Authors: Fonck C, Damaj M, Deshpande P, Bowers B, Wehner J, Nashimi R, et al.
  Yr: 2001 Vol: Nbr: Abs: Pg:
Characterization of alpha4 beta2 nicotinic receptor-fluorescent protein chimeras.
Periodical:Society for Neuroscience Abstracts Index Medicus: Soc Neurosci (Abs)
  Authors: Nashmi R, Dickinson M, McKinney S, Labarca C, Fraser S, Lester H
  Yr: 2002 Vol: Nbr: Abs: Pg:
Seizure and straub tail responses in knock-in mice carrying hypersensitive neuronal nicotinic receptors.
Periodical:Society for Neuroscience Abstracts Index Medicus: Soc Neurosci (Abs)
  Authors: Fonck C, Nashmi R, Labarca C, Deshpande P, Lester H
  Yr: 2002 Vol: Nbr: Abs: Pg:
Fluorescence energy transfer (FRET) between functional alpha4beta2 nicotinic acetylcholine receptor (nAChR) subunits.
Periodical:Biophysical Society Abstracts Index Medicus:
  Authors: Nashmi R, Dickinson M, McKinney S, Jareb M, Labarca C, Fraser S, Lester H
  Yr: 2003 Vol: Nbr: Abs: Pg:
Localization, trafficking and resonance energy transfer in alpha4beta2 nicotinic receptor-fluorescent protein chimeras.
Periodical:Society for Research on Nicotine and Tobacco Conference Index Medicus:
  Authors: Nashmi R, Dickinson M, McKinney S, Jareb M, Labarca C, Fraser S, Lester H
  Yr: 2003 Vol: Nbr: Abs: Pg: