The addiction to use of tobacco products is one of the most common and most destructive addictions in the world today. It is estimated that nearly half of the world population smokes cigarettes. Few of the biological markers commonly used to monitor smoking cessation provide information on long term use of tobacco products, nor any type of prediction of success in quitting the smoking habit. We have shown that nicotinic acetylcholine receptors, the receptors responding to nicotine in cigarettes, are increased in postmortem brain of subjects who were smokers in life, but decline to near control values in subjects who had ceased to smoke for varying periods before death. Nicotinic receptors are also expressed in the white cells of peripheral blood, which is easy to obtain in a clinical setting. Peripheral blood neutrophils have a similar regulatory response to use of tobacco products as is seen in brain. The proposed studies would develop the assay for nicotinic receptor levels in peripheral blood as a biological marker for monitoring smoking cessation. We will 1) optimize the nicotinic receptor binding assay for peripheral blood neutrophils, 2) determine the range of nicotinic receptor expression in blood neutrophils in never-smokers and in subjects with variable smoking histories, and 3) evaluate the utility of this assay in an actual smoking cessation program.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA012281-02
Application #
2898307
Study Section
Special Emphasis Panel (ZDA1-KXN-G (08))
Program Officer
Gordon, Harold
Project Start
1998-09-30
Project End
2001-08-31
Budget Start
1999-09-01
Budget End
2000-08-31
Support Year
2
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Colorado Denver
Department
Psychiatry
Type
Schools of Medicine
DUNS #
065391526
City
Aurora
State
CO
Country
United States
Zip Code
80045
Mexal, S; Berger, R; Adams, C E et al. (2006) Brain pH has a significant impact on human postmortem hippocampal gene expression profiles. Brain Res 1106:1-11
Mexal, S; Frank, M; Berger, R et al. (2005) Differential modulation of gene expression in the NMDA postsynaptic density of schizophrenic and control smokers. Brain Res Mol Brain Res 139:317-32
Gault, Judith; Hopkins, Janet; Berger, Ralph et al. (2003) Comparison of polymorphisms in the alpha7 nicotinic receptor gene and its partial duplication in schizophrenic and control subjects. Am J Med Genet B Neuropsychiatr Genet 123B:39-49
Lee, M J; Breese, C R; Strook, M L et al. (2001) The effect of nicotine and haloperidol co-treatment on nicotinic receptor levels in the rat brain. Brain Res Mol Brain Res 86:115-24
Weiland, S; Bertrand, D; Leonard, S (2000) Neuronal nicotinic acetylcholine receptors: from the gene to the disease. Behav Brain Res 113:43-56
Benhammou, K; Lee, M; Strook, M et al. (2000) [(3)H]Nicotine binding in peripheral blood cells of smokers is correlated with the number of cigarettes smoked per day. Neuropharmacology 39:2818-29
Breese, C R; Lee, M J; Adams, C E et al. (2000) Abnormal regulation of high affinity nicotinic receptors in subjects with schizophrenia. Neuropsychopharmacology 23:351-64