p450 - publications

Predict more p450 - ligand interactions now!

1. Neuroimage. 2012 Feb 3. [Epub ahead of print]

Genetic variation in CYP2A6 predicts neural reactivity to smoking cues as
measured using fMRI.

Tang DW, Hello B, Mroziewicz M, Fellows LK, Tyndale RF, Dagher A.

Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill
University, 3801 University St, Room WB 214D, Montreal, QC, Canada H3A 2B4;
Department of Psychology, McGill University, 1205 Dr. Penfield Ave, Montreal, QC,
Canada H3A 1B1.

Smoking cues trigger craving for cigarettes and relapse. Nicotine metabolism,
mediated by the enzyme CYP2A6, also influences smoking behavior. In this study,
we investigated how nicotine metabolism and genetic variation in CYP2A6 influence
the neural response to smoking cues in humans using functional magnetic resonance
imaging (fMRI). We hypothesized that individuals with faster rates of nicotine
metabolism would have stronger conditioned responses to smoking cues because of
closer coupling in everyday life between exposure to cigarettes and surges in
blood nicotine concentration. In contrast, individuals with reduced rates of
metabolism, who have relatively constant nicotine blood levels throughout the
day, should be less likely to develop conditioned responses to cues. We screened
169 smokers for their rate of nicotine metabolism and CYP2A6 genotype, and
selected 31 smokers with the fastest and slowest rates for fMRI, matched for
daily cigarette intake. We measured their neural response to visual smoking and
non-smoking cues using fMRI. As predicted, fast metabolizers, by phenotype or
genotype, had significantly greater responses to visual cigarette cues than slow
metabolizers in the amygdala, hippocampus, striatum, insula, and cingulate
cortex. These results support the theory that drug cues are conditioned stimuli,
and explain why fast metabolizers who smoke have lower cessation rates. They also
provide insight into how genetics can shape human vulnerability to addiction, and
have implications for tailoring smoking cessation programs based on individual

Copyright © 2012. Published by Elsevier Inc.

PMID: 22342802 [PubMed - as supplied by publisher]