Nicotine Reinforcement and Smoking-Cue Reactivity: Association With Genetic Polymorphisms
Condition: Nicotine Dependence
MeSH terms: Tobacco Use Disorder
Study type: Observational

Summary: 
      Background:

      - Researchers have been studying behavioral components of nicotine addiction by looking at
      how drugs have a reinforcing effect, connecting the stimulation provided by the drug
      (nicotine) to the behavior that produces it (smoking). Based on previous studies, researchers
      are interested in learning more about how nicotine affects current smokers' responses to
      psychological tests and smoking-related cues, and in studying whether certain kinds of
      genetic background may affect smokers' responses to these kinds of studies.

      Objectives:

        -  To compare the effect of nicotine versus denicotinized cigarettes during specific
           psychological tests.

        -  To compare the effects of smoking cues versus neutral cues on craving, mood, and
           autonomic response.

        -  To study the effect of genes on nicotine reinforcement and smoking-cue reactivity.

      Eligibility:

      - Individuals between 18 and 64 years of age who are current smokers (at least 10 cigarettes
      per day for at least 1 year) and are not currently interested in reducing their smoking or
      seeking treatment for tobacco dependence.

      Design:

        -  Pilot session:

        -  Participants will practice smoking using the measuring equipment that will be used in
           the study.

        -  After successful practice, participants will read or listen to music for 1 hour, during
           which they are not allowed to smoke.

        -  After the 1-hour period, participants will sample study cigarettes that have different
           levels of nicotine, and will be asked to guess whether the cigarettes are normal study
           cigarettes or denicotinized cigarettes.

        -  Baseline session:

        -  Blood, urine, and breath samples will be taken at the start of the session.

        -  Participants will smoke part of an initial cigarette, and then will read or listen to
           music for 1 hour, during which they are not allowed to smoke.

        -  After the 1-hour period, participants will give another breath sample and will complete
           questionnaires about mood and concentration levels.

        -  Trial sessions:

        -  Participants will smoke study cigarettes, and will be asked to either respond to
           questions about perceived nicotine levels in the cigarettes or press a lever for the
           chance to be rewarded with additional puffs of the cigarette. After the session,
           participants will give another breath sample and will complete questionnaires about mood
           and concentration levels.

        -  Participants will also participate in cue-reactivity sessions to test the body's
           physiological response to smoking cues (a pack of cigarettes) and neutral cues (a pack
           of unsharpened pencils). After the session, participants will complete questionnaires on
           mood and concentration 15, 30, 45, and 60 minutes after the session.

        -  At the conclusion of the last experimental session, participants will discuss the study
           with researchers, and may receive a referral list of smoking treatment programs.
    

Detailed description: 
      Objectives: 1) to compare the reinforcing efficacy of nicotine versus denicotinized
      cigarettes using a forced choice and an operant response procedure, 2) to compare the effects
      of smoking cues versus neutral cues on craving, mood, and autonomic responsivity, and 3) to
      explore potential associations between several genetic polymorphisms and the phenotypic
      measures of nicotine reinforcement and smoking-cue reactivity.

      Study population: 175 adult smokers (35 for pilot study I, 60 for pilot stufy II and 80 for
      main study).

      Design: Placebo-controlled, within-subjects design. Pilot studies will entail 1-2 sessions.
      Main study will entail one baseline/adaptation session and 5-10 experimental sessions.

      Outcome Measures:

      Behavioral Measures

      During forced-choice sessions, primary measure is the percentage of nicotine cigarette puffs
      chosen and taken during choice trials. During operant response sessions, primary measures
      include breakpoint (final ratio completed), total number of responses, and number of
      cigarette puffs earned and taken. During cue-reactivity sessions, primary measures include
      craving, mood, and autonomic responsivity (heart rate, blood pressure, skin conductance, and
      skin temperature).

      Genetic Measures

      The following genetic polymorphisms will be assayed: 1) C/T rs2023239 variant of the CB1R
      gene, 2) the Ser/Gly rs6280 variant of DRD3 gene, and 3) variants of the CYP2A6 gene.

      Secondary Measures

      Secondary study measures include baseline smoking history, FTND, TCQ-SF, mood form, CO, and
      urinary cotinine and 3-hydroxycotinine. The ratio of 3-hydroxycotinine/cotinine is a
      phenotypic biomarker of the rate of nicotine metabolism, which has been shown to be
      associated with CYP2A6 genotype, level of nicotine dependence, various smoking behaviors, and
      treatment outcome.
    

Time perspective: Other
Keywords: Nicotine Reinforcement; Tobacco Craving; Behavior Genetics; Smoking