Contemporary models of addiction highlight the probable involvement of brain reward mechanisms mediated largely via dopaminergic (DA) connections between the midbrain (ventral tegmental area) and prefrontal cortex. There is animal and human data indicating that activity in these pathways is compromised during acute abstinence from addictive substances, and that associated behavioral functions, including incentive motivation, reactivity to drug-related cues, and executive cognitive processes, are also impaired. The present study extends this evidence with new and more extensive measures to investigate the extent to which these functions recover over three months of abstinence in smokers. It also tests the hypothesis that impairments of impulse control and incentive motivation seen during acute abstinence increase relapse risk. Impaired incentive motivation may decrease the ability to stop smoking by reducing the person's capacity to enjoy or seek out alternative non-drug rewards. Finally, impairments seen during abstinence may represent genetic differences in brain DA pathways rather than smoking-induced abnormalities. All these issues are addressed using an experimental between- and within-subjects design in which smokers are randomly allocated to a quit group (n=150) or a non-quit group (n=50). The quit participants will be required to abstain from smoking and from nicotine replacement therapy, with compliance verified via salivary cotinine testing. Smoking characteristics, dopamine-related genotypes (including DRD4, DRD2, and DATI), and personality measures relating to impulsivity (e.g. Novelty- Seeking) will be measured at baseline, and cognitive and behavioral assessments will then be conducted up to six times over the following three months. For those quit participants who remain abstinent for part or all of the period (approximately 75 at a week, 45 at a month, and 20-330 at 3 months), any recovery of functioning will be distinguishable from practice effects shown by the non-quit group. Abstinence-related impairment indices for each measure will be derived for each participant by conducting two assessments prior to randomization: both assessments will be preceded by 10 hours abstinence from smoking, and participants will receive subcutaneous injection of nicotine prior to one assessment and of placebo prior to the other (counterbalanced order). Correlational and multivariate analyses will investigate the relationships between these impairments, speed/severity of relapse, and genotypes.
| Dawkins, Lynne; Powell, Jane H; Pickering, Alan et al. (2009) Patterns of change in withdrawal symptoms, desire to smoke, reward motivation and response inhibition across 3 months of smoking abstinence. Addiction 104:850-8 |
| Powell, J H; Pickering, A D; Dawkins, L et al. (2004) Cognitive and psychological correlates of smoking abstinence, and predictors of successful cessation. Addict Behav 29:1407-26 |
