Animal and human studies will be conducted in parallel to determine the threshold dosing for the first symptoms of nicotine dependence in adolescent humans and for the first neurochemical changes brought on by nicotine in the brains of adolescent rats. Separate experiments will evaluate the upregulation of high affinity nicotinic cholinergic receptors in the midbrain reward centers, and the activation of cholinergic reward pathways. These experiments will be conducted to explore the effects of low-dose intermittent exposure to nicotine, simulating the nicotine exposures commonly present at the onset of nicotine dependence in teenagers. A comparison will be made regarding the sensitivity of adolescent and adult rats to the neurochemical effects of nicotine that are thought to be responsible for dependence. Intermittent and continuous dosing will be compared and gender differences will be explored. Adolescents and adults will be compared in the speed with which neurochemical changes occur. In humans, a prospective longitudinal study employing 1200 subjects and individual interviews will be conducted to explore individual differences in the speed with which nicotine dependence develops. The nicotine dosing and pattern of use at the onset of the first symptoms and full dependence will be studied. Investigations will explore why some youths develop symptoms of dependence upon exposure to nicotine while others do not. A new theory-based measure of early dependence for youths will be tested against established measures of dependence.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA014666-04
Application #
6806571
Study Section
Special Emphasis Panel (ZDA1-MXG-S (01))
Program Officer
Hoffman, Allison
Project Start
2001-09-30
Project End
2006-08-31
Budget Start
2004-09-10
Budget End
2005-08-31
Support Year
4
Fiscal Year
2004
Total Cost
$388,970
Indirect Cost
Name
University of Massachusetts Medical School Worcester
Department
Family Medicine
Type
Schools of Medicine
DUNS #
603847393
City
Worcester
State
MA
Country
United States
Zip Code
01655
DiFranza, Joseph R; Savageau, Judith A; Fletcher, Kenneth et al. (2007) Susceptibility to nicotine dependence: the Development and Assessment of Nicotine Dependence in Youth 2 study. Pediatrics 120:e974-83
DiFranza, Joseph R; Savageau, Judith A; Fletcher, Kenneth et al. (2007) Symptoms of tobacco dependence after brief intermittent use: the Development and Assessment of Nicotine Dependence in Youth-2 study. Arch Pediatr Adolesc Med 161:704-10
DiFranza, Joseph R; Wellman, Robert J (2007) Sensitization to nicotine: how the animal literature might inform future human research. Nicotine Tob Res 9:9-20
Wellman, Robert J; Savageau, Judith A; Godiwala, Sameer et al. (2006) A comparison of the Hooked on Nicotine Checklist and the Fagerstrom Test for Nicotine Dependence in adult smokers. Nicotine Tob Res 8:575-80
Wellman, Robert J; DiFranza, Joseph R; Savageau, Judith A et al. (2006) The effect of abstinence on cigarette consumption upon the resumption of smoking. Addict Behav 31:711-6
Wellman, Robert J; DiFranza, Joseph R; Wood, Constance (2006) Tobacco chippers report diminished autonomy over smoking. Addict Behav 31:717-21
Fernando, W W S A; Wellman, Robert J; Difranza, Joseph R (2006) The relationship between level of cigarette consumption and latency to the onset of retrospectively reported withdrawal symptoms. Psychopharmacology (Berl) 188:335-42
Wellman, Robert J; DiFranza, Joseph R; Savageau, Judith A et al. (2005) Measuring adults' loss of autonomy over nicotine use: the Hooked on Nicotine Checklist. Nicotine Tob Res 7:157-61
DiFranza, Joseph R; Wellman, Robert J (2005) A sensitization-homeostasis model of nicotine craving, withdrawal, and tolerance: integrating the clinical and basic science literature. Nicotine Tob Res 7:9-26