Investigations on nicotine-stimulated neuropeptide release from cigarette smoking suggest mechanisms involving positive reinforcement or rewarding processes which might explain the discriminative control of smoking by stimuli dependent of the nicotine-addiction cycle. We shall attempt to demonstrate experimentally, using behavioral markers and biochemical measurements, the contribution of one neuropeptide -- Beta-endorphin -- to the reinforcement of smoking. The basic approach involves a repeated-measures within subjects design, with different experimental conditions studied over successive days and simultaneous measurement of subjective, behavioral, physiological, and biochemical variables.
The specific aims of the research are: I) to demonstrate the effects of nicotine intake from smoking on relevant behavioral markers of cholinergic/Beta-endorphinergic activity (cold-water pain and puzzle anxiety); II) to determine whether pain-reduction (antinociception) from smoking is due to the termination of nicotine-withdrawal or to nicotine effects independent of withdrawal; III) to establish whether the frequency or intensity of cigarette smoking is increased by a dysphoric state not associated with the nicotine-addiction cycle, such as anxiety; IV) to sort out the relative contribution of nicotinic cholinergic activity and Beta-endorphinergic activity on pain and anxiety responses through the administration of a cholinergic blocker (mecamylamine), an opiate antagonist (naloxone), or synthetic Beta-endorphin. The project has its long-term research objective the integration of behavioral (psychological) research on nicotine and smoking with biochemical (neuroendocrinological and psychopharmacological) investigations of neuropeptide activity at the normal human level. The health implicatons are that a better understanding of underlying biobehavioral mechanisms in smoking and substance abuse may make possible the development of rational therapies of greater effectiveness than are currently available.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA042730-02
Application #
3184241
Study Section
Drug Abuse Clinical and Behavioral Research Review Committee (DACB)
Project Start
1985-08-16
Project End
1987-03-31
Budget Start
1986-04-01
Budget End
1987-03-31
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Type
Schools of Medicine
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Pomerleau, Ovide F; Pomerleau, Cynthia S; Snedecor, Sandy M et al. (2004) Depression, smoking abstinence and HPA function in women smokers. Hum Psychopharmacol 19:467-76
Pomerleau, Ovide F; Fagerstrom, Karl-Olov; Marks, Judith L et al. (2003) Development and validation of a self-rating scale for positive- and negative-reinforcement smoking: The Michigan Nicotine Reinforcement Questionnaire. Nicotine Tob Res 5:711-8
Pomerleau, Ovide F; Pomerleau, Cynthia S; Marks, Judith L et al. (2003) Prolonged nicotine patch use in quitters with past abstinence-induced depressed mood. J Subst Abuse Treat 24:13-8
Pomerleau, Cynthia S; Zucker, Alyssa N; Stewart, Abigail J (2003) Patterns of depressive symptomatology in women smokers, ex-smokers, and never-smokers. Addict Behav 28:575-82
Hudmon, Karen Suchanek; Marks, Judith L; Pomerleau, Cynthia S et al. (2003) A multidimensional model for characterizing tobacco dependence. Nicotine Tob Res 5:655-64
Pomerleau, C S; Brouwer, R J; Pomerleau, O F (2001) Emergence of depression during early abstinence in depressed and non-depressed women smokers. J Addict Dis 20:73-80
Pomerleau, C S; Marks, J L; Pomerleau, O F (2000) Who gets what symptom? Effects of psychiatric cofactors and nicotine dependence on patterns of smoking withdrawal symptomatology. Nicotine Tob Res 2:275-80
Pomerleau, C S; Mehringer, A M; Marks, J L et al. (2000) Effects of menstrual phase and smoking abstinence in smokers with and without a history of major depressive disorder. Addict Behav 25:483-97
Pomerleau, C S; Pomerleau, O F; Namenek, R J et al. (2000) Short-term weight gain in abstaining women smokers. J Subst Abuse Treat 18:339-42
Marks, J L; Pomerleau, C S; Pomerleau, O F (1999) Effects of menstrual phase on reactivity to nicotine. Addict Behav 24:127-34

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