Genetic factors play a considerable role in nicotine addiction. The present proposal addresses the molecular neuroadaptive processes that mediate the switch from initial nicotine exposure to addiction. Inbred mouse strains, which are highly sensitive to acute nicotine exposure, develop tolerance to chronic nicotine and provide a model for examining the mechanisms underlying the switch from acute nicotine exposure to addiction. C3H, DBA/2, and C57BL/6 mice represent low-, moderate-, and high-nicotine sensitive strains, respectively. Alterations in nicotinic acetylcholine receptors only partially explain the differential effects of acute and chronic nicotine in these strains. Nicotine modulates multiple neurotransmitter systems. The present proposal examines the molecular neuroadaptations in neurotransmitters that occur after acute and chronic nicotine exposure in C3H, DBA/2, and C57BL/6 mice. C3H, DBA/2, and C57BL/6 mice will be continuously infused with nicotine or saline for 6 hr or 10 days. Whole brain will be removed and mRNA phenotype assessed by gene microarray and expression changes validated by quantitative RT-PCR and in situ hybridization. Genotypic and phenotypic changes in mRNA expression in neurotransmitter biochemical pathways will be characterized. Determination of the differential effects of acute and chronic nicotine on gene expression may provide insight into the molecular neuroadaptations that underlie the switch from acute nicotine exposure to nicotine addiction in humans.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32DA015591-01A1
Application #
6648102
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Babecki, Beth
Project Start
2003-09-01
Project End
2003-12-31
Budget Start
2003-09-01
Budget End
2003-12-31
Support Year
1
Fiscal Year
2003
Total Cost
$12,425
Indirect Cost
Name
University of Colorado Denver
Department
Psychiatry
Type
Schools of Medicine
DUNS #
041096314
City
Aurora
State
CO
Country
United States
Zip Code
80045
Frank, Matthew G; Watkins, Linda R; Maier, Steven F (2013) Stress-induced glucocorticoids as a neuroendocrine alarm signal of danger. Brain Behav Immun 33:1-6
Frank, Matthew G; Thompson, Brittany M; Watkins, Linda R et al. (2012) Glucocorticoids mediate stress-induced priming of microglial pro-inflammatory responses. Brain Behav Immun 26:337-45
Holguin, Adelina; Frank, Matthew G; Biedenkapp, Joseph C et al. (2007) Characterization of the temporo-spatial effects of chronic bilateral intrahippocampal cannulae on interleukin-1beta. J Neurosci Methods 161:265-72
Frank, Matthew G; Der-Avakian, Andre; Bland, Sondra T et al. (2007) Stress-induced glucocorticoids suppress the antisense molecular regulation of FGF-2 expression. Psychoneuroendocrinology 32:376-84
Frank, Matthew G; Barrientos, Ruth M; Biedenkapp, Joseph C et al. (2006) mRNA up-regulation of MHC II and pivotal pro-inflammatory genes in normal brain aging. Neurobiol Aging 27:717-22
Frank, Matthew G; Wieseler-Frank, Julie L; Watkins, Linda R et al. (2006) Rapid isolation of highly enriched and quiescent microglia from adult rat hippocampus: immunophenotypic and functional characteristics. J Neurosci Methods 151:121-30
Milligan, Erin D; Sloane, Evan M; Langer, Stephen J et al. (2005) Controlling neuropathic pain by adeno-associated virus driven production of the anti-inflammatory cytokine, interleukin-10. Mol Pain 1:9