Our research to date has demonstrated that cigarette smokers exhibit enhanced basal hypothalamic-pituitary-adrenocortical (HPA) activity and attenuated cortisol responses to multiple stress procedures. Our particularly important finding has been that this altered stress response predicts early smoking relapse. It is well-established that the endogenous opioid system plays a critical role in HPA regulation and that both systems are involved in regulating mood and reinforcing effects of drug use. The extent to which altered HPA response in smokers is due to disrupted endogenous opioid regulation is unknown and is the focus of the proposed research. Preliminary findings on the effects of opioid blockade on HPA stress response indicate that diminished opioid tone may be one potentially important mechanism. The extent to which these opioid-HPA alterations are modified by smoking abstinence and the extent to which they exacerbate symptoms associated with abstinence will be elucidated by this research. We have also demonstrated sex differences with respect to relapse predictors. The proposed research will examine and clarify sex differences in hormonal response patterns during an opioid blockade challenge and in response to stress in dependent female and male smokers. In combination, the findings to date and the potential discovery of an important pathway for stress effects on smoking point to the importance of delineating the opioid-HPA interactions. Confirmation of dysregulated endogenous opioid tone in abstinent smokers and in response to stress will set the stage for refined investigations to develop biobehavioral markers of nicotine dependence, stress-related craving, and relapse.

Public Health Relevance

Tobacco addiction/dependence is the leading preventable cause of cancer and cardiovascular diseases. Stress is widely cited as a reason for continued smoking and for relapse in those attempting to achieve long term abstinence. The proposed research extends our program to identify biobehavioral mechanisms and determinants of stress effects on smoking. This will set the stage for research to determine relapse vulnerability markers. In turn, this will provide unique opportunities for prediction and development of targeted interventions.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA016351-08
Application #
8528529
Study Section
Special Emphasis Panel (ZRG1-BBBP-T (02))
Program Officer
Gordon, Harold
Project Start
2003-04-01
Project End
2014-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
8
Fiscal Year
2013
Total Cost
$300,849
Indirect Cost
$101,611
Name
University of Minnesota Twin Cities
Department
Type
Schools of Medicine
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Wiggert, Nicole; Wilhelm, Frank H; Nakajima, Motohiro et al. (2016) Chronic Smoking, Trait Anxiety, and the Physiological Response to Stress. Subst Use Misuse 51:1619-1628
Lemieux, Andrine; Olson, Leif; Nakajima, Motohiro et al. (2016) Life adversity is associated with smoking relapse after a quit attempt. Addict Behav 60:71-7
Bongard, Stephan; Olson, Leif; Nakajima, Motohiro et al. (2016) Anger Expression Style Predicts the Domain of the First Smoking Relapse After a Quit Attempt. Subst Use Misuse 51:1810-4
al'Absi, Mustafa; Nakajima, Motohiro; Allen, Sharon et al. (2015) Sex differences in hormonal responses to stress and smoking relapse: a prospective examination. Nicotine Tob Res 17:382-9
Lemieux, Andrine; Nakajima, Motohiro; Hatsukami, Dorothy K et al. (2015) Changes in circulating leptin levels during the initial stage of cessation are associated with smoking relapse. Psychopharmacology (Berl) 232:3355-61
Baingana, Florence; al'Absi, Mustafa; Becker, Anne E et al. (2015) Global research challenges and opportunities for mental health and substance-use disorders. Nature 527:S172-7
al'Absi, Mustafa; Lemieux, Andrine; Nakajima, Motohiro et al. (2015) Circulating leptin and pain perception among tobacco-dependent individuals. Biol Psychol 107:10-5
Nakajima, Motohiro; Al'Absi, Mustafa (2014) Nicotine withdrawal and stress-induced changes in pain sensitivity: a cross-sectional investigation between abstinent smokers and nonsmokers. Psychophysiology 51:1015-22
al'Absi, Mustafa; Lemieux, Andrine; Nakajima, Motohiro (2014) Peptide YY and ghrelin predict craving and risk for relapse in abstinent smokers. Psychoneuroendocrinology 49:253-9
Potretzke, Sheena; Nakajima, Motohiro; Cragin, Tiffany et al. (2014) Changes in circulating leptin levels during acute stress and associations with craving in abstinent smokers: a preliminary investigation. Psychoneuroendocrinology 47:232-40

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