Recent animal research indicates acute nicotine increases the reinforcing effects of other rewards;however, chronic use of nicotine recruits an opponent process that counteracts the acute effects of nicotine and decreases sensitivity to rewards. When nicotine is discontinued in animals, this opponent process persists and the resultant decreased sensitivity to rewards may be a cause of nicotine withdrawal symptoms such as depression and a cause of relapse back to smoking. Although this animal model is widely cited, whether decreased reward sensitivity occurs when smokers stop smoking is unclear. The investigators propose an experimental test that focuses on whether abstinent smokers a) are less sensitive to monetary rewards during an operant task and/or b) report anhedonia (less pleasure from rewards) and apathy (less motivation to seek rewards). The investigators will recruit 120 current smokers who plan to quit smoking for good to smoke their usual amount for one week and then will abstain for 4 weeks. To insure an adequate number of continuously abstinent smokers and to decrease selection bias, they will use monetary contingencies to encourage abstinence. The investigators anticipate this will produce >70 smokers who remain abstinent for all 4 weeks. To assist in interpretation of results, they will also recruit a comparison group of 70 long-abstinent former smokers to be measured on the same schedule. The investigators will measure reward sensitivity three times each week using a) progressive ratio (PR) responding for monetary rewards and b) self-report measures of anhedonia and apathy scales. If reward sensitivity changes with abstinence, secondary aims will be to determine a) its magnitude, incidence and time course;b) whether it exhibits the time course expected of a withdrawal effect, c) whether reward sensitivity becomes similar to the level among long-abstinent smokers and c) whether decreased reward sensitivity could be the basis for much of withdrawal discomfort. The results of this study will be an important translational test of the leading animal model of nicotine withdrawal. If decreased reward sensitivity is found, this would suggest revisions in clinical descriptions of nicotine withdrawal, new targets for behavioral and pharmacological interventions and new treatments for smoking cessation (e.g., increased exposure to rewarding events). If reward sensitivity does not change with abstinence, then (given the adequacy of the investigators'test) this would suggest a widely cited animal model of abstinence effects may not be generalizable to human attempts to stop smoking.

Public Health Relevance

The most widely-accepted animal model of nicotine withdrawal states stopping nicotine makes rewarding events become less rewarding. The current study will test if this is true in humans. If the investigators find tobacco abstinence does make rewards less rewarding, this would suggest new symptoms to add to official descriptions of nicotine withdrawal. It would also suggest the need to develop new behavioral and pharmacological interventions to correct this problem. If stopping smoking does not make rewards less rewarding, this would suggest that this animal model does not apply to the human condition and a need to continue the search for an animal model of tobacco withdrawal that is relevant to smokers'stopping smoking.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA031687-03
Application #
8462234
Study Section
Risk, Prevention and Intervention for Addictions Study Section (RPIA)
Program Officer
Kautz, Mary A
Project Start
2011-08-15
Project End
2015-01-31
Budget Start
2014-02-01
Budget End
2015-01-31
Support Year
3
Fiscal Year
2014
Total Cost
$581,712
Indirect Cost
$98,597
Name
University of Vermont & St Agric College
Department
Psychiatry
Type
Schools of Medicine
DUNS #
066811191
City
Burlington
State
VT
Country
United States
Zip Code
05405