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Influence of individual nicotine metabolism rate on cognitive effects of nicotine withdrawal.
- Format:
- Book
- Thesis/Dissertation
- Author/Creator:
- Falcone, Mary K.
- Language:
- English
- Subjects (All):
- Pharmacology.
- 0419.
- Penn dissertations--Pharmacology.
- Pharmacology--Penn dissertations.
- Local Subjects:
- Penn dissertations--Pharmacology.
- Pharmacology--Penn dissertations.
- 0419.
- Physical Description:
- 160 pages
- Contained In:
- Dissertation Abstracts International 74-10B(E).
- System Details:
- Mode of access: World Wide Web.
- text file
- Summary:
- Chronic nicotine exposure leads to neurobiological changes, and nicotine withdrawal is associated with a decline in cognitive performance as well as cravings for cigarettes. Faster metabolism of nicotine has been associated with increased risk of relapse among smokers trying to quit. I hypothesized that faster nicotine metabolism would be associated with increased cognitive withdrawal symptoms. To evaluate this hypothesis, I examined relationships between individual nicotine metabolite ratio (3'-hydroxycotinine/cotinine; NMR), abstinence and brain activation during an n-back task assessing working memory performance and a cue reactivity task. Seventy-three smokers completed blood-oxygenation-level dependent (BOLD) functional magnetic resonance imaging (fMRI) scans on two separate occasions: one after smoking as usual and one after 24 hours of biochemically confirmed abstinence (order randomized and counterbalanced). For the n-back task, abstinence (versus smoking) led to reduced accuracy, slower median correct response time, and reduced BOLD signal change in the medial frontal/cingulate gyrus and right and left dorsolateral prefrontal cortex (DLPFC). There were no significant NMR by session interaction effects or main effects of NMR on behavioral performance. However, in the left DLPFC, abstinence was associated with greater reductions in activation in slower metabolizers than in faster metabolizers (NMR by session interaction, p = 0.008); this is in the opposite direction of the hypothesis. In the posterior cingulate cortex (PCC) and ventromedial prefrontal cortex (vmPFC), abstinence was associated with less suppression of activation in faster metabolizers than in slower metabolizers (p for interaction effect = 0.005 and 0.0002 respectively). Although this is consistent with my hypothesis, in combination with the absence of a behavioral effect and the inconsistent directionality of the NMR effect in the task-positive and task-negative networks it does not provide evidence of greater abstinence-induced working memory deficits in faster metabolizers. For the cue reactivity task, craving was positively associated with abstinence (p < 0.001) and faster metabolism rate (p = 0.021); however, the NMR by session interaction was nonsignificant. In the ROI analysis, faster metabolism was associated with greater cue reactivity (smoking cue BOLD response minus neutral image BOLD response) in the vmPFC (p = 0.013) in both sessions. There were no main effects of NMR in the right or left anterior insula, the dorsal anterior cingulate cortex, the left midtemporal gyrus, or the PCC/precuneus, and there were no NMR by session interaction effects in any ROI. These data do not support the hypothesis that individuals who metabolize nicotine faster experience greater cognitive effects or cue reactivity during acute nicotine withdrawal. Other potential mechanisms, such as differences in nicotine reward and nicotinic receptor regulation, warrant attention as potential mediators of the relationship of nicotine metabolism rate to smoking relapse.
- Notes:
- Thesis (Ph.D. in Pharmacology) -- University of Pennsylvania, 2013.
- Source: Dissertation Abstracts International, Volume: 74-10(E), Section: B.
- Adviser: Caryn Lerman.
- Local Notes:
- School code: 0175.
- ISBN:
- 9781303145513
- Access Restriction:
- Restricted for use by site license.
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