Smoking is responsible for over 400,000 premature deaths and $50 Billion of medical costs in the USA each year. An estimated 70% of smokers want to quit, however only 2.5% succeed in quitting each year. Nicotine is believed to be the main reinforcing and addicting component in tobacco smoke, however the rewarding mechanism of nicotine is poorly understood. A greater understanding of nicotine's effects within the brain will identify novel targets for smoking cessation therapies. Electrophysiological studies have implicated both the B2- and a7-containing nicotinic acetylcholine receptors (nAChRs) in nicotine-induced release of dopamine (DA) within the mesolimbic DA system. This release of DA is thought to be critical for nicotine reinforcement, however the contributions of the beta2 and alpha nAChR subunits have not been examined in a behavioral model of nicotine reward. Toward this end, I propose self-administration studies using beta2 and alpha7 nAChR subunit knockout and transgenic mice to determine their respective contributions to nicotine reward. In addition, I will study whether nicotine alters cocaine- and amphetamine-regulated transcript (CART) expression, a neuropeptide with high levels of expression in the nucleus accumbens and hypothalamus. CART expression is increased with cocaine or amphetamine administration. CART has been shown to have reinforcing properties, to decrease food intake, and to induce anxiety. CART knockout mice will also undergo nicotine self-administration experiments to determine if CART is necessary for nicotine reinforcement.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
1F31DA019298-01
Application #
6885012
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Babecki, Beth
Project Start
2005-01-03
Project End
2007-01-02
Budget Start
2005-01-03
Budget End
2006-01-02
Support Year
1
Fiscal Year
2005
Total Cost
$25,022
Indirect Cost
Name
Yale University
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
El-Hage, Nazira; Podhaizer, Elizabeth M; Sturgill, Jamie et al. (2011) Toll-like receptor expression and activation in astroglia: differential regulation by HIV-1 Tat, gp120, and morphine. Immunol Invest 40:498-522
Steiner, Rebecca C; Heath, Christopher J; Picciotto, Marina R (2007) Nicotine-induced phosphorylation of ERK in mouse primary cortical neurons: evidence for involvement of glutamatergic signaling and CaMKII. J Neurochem 103:666-78
Steiner, Rebecca C; Hsiung, Hansen M; Picciotto, Marina R (2006) Cocaine self-administration and locomotor sensitization are not altered in CART knockout mice. Behav Brain Res 171:56-62