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DRD4 VNTR polymorphism is associated with transient fMRI-BOLD responses to smoking cues

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Abstract

Rationale

A dopamine receptor 4 variable number tandem repeat (DRD4 VNTR) polymorphism has been related to reactivity to smoking cues among smokers, but the effect of this genetic variation on brain responses to smoking cues has not been evaluated.

Objectives

The present study evaluated the relationship between carrying the DRD4 VNTR 7-repeat allele and transient functional magnetic resonance imaging (fMRI) blood-oxygen-level-dependent responses to smoking cues among adult dependent cigarette smokers.

Materials and methods

Smokers (n = 15) underwent fMRI scanning after 2-h abstinence. During scanning, they viewed visual smoking and control cues. A blood sample was assayed for the DRD4 VNTR polymorphism, and participants were categorized based on whether they carried one or two copies of the 7-repeat allele (DRD4 L, n = 7) or not (DRD4 S, n = 8).

Results

Contrasts in brain cue-reactivity (smoking minus control cues) between DRD4 groups were conducted using SPM2. Smoking cues as compared to control cues elicited transient brain responses in right superior frontal gyrus (BA 8/9/10/32), left anterior cingulate gyrus (BA 32), and right cuneus (BA 19). Exposure to smoking cues resulted in greater activation of right superior frontal gyrus (BA 10) and right insula in DRD4 L compared to DRD4 S individuals. By contrast, exposure to smoking cues among DRD4 S individuals resulted in no significant increases in activation compared to DRD4 L individuals.

Conclusions

These brain imaging results suggest that DRD4 VNTR polymorphism is related to transient brain responses to smoking cues in regions subserving executive and somatosensory processes.

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Acknowledgements

The authors wish to thank Mr. Berry Hiott for collection of fMRI data and Dr. Scott Kollins for his comments on an earlier version of this manuscript. This research supported by NIDA K23DA017261 (FJM), NIAAA R01AA012238-07 (KEH), and an unrestricted donation from Vector Tobacco Co. (JER).

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Authors and Affiliations

  1. Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Box 2701, Durham, NC, 27708, USA

    F. Joseph McClernon, Jed E. Rose & Rachel V. Kozink

  2. Department of Psychology, University of Colorado at Boulder, Boulder, CO, USA

    Kent E. Hutchison

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  1. F. Joseph McClernon
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  2. Kent E. Hutchison
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  3. Jed E. Rose
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  4. Rachel V. Kozink
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Correspondence to F. Joseph McClernon.

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McClernon, F.J., Hutchison, K.E., Rose, J.E. et al. DRD4 VNTR polymorphism is associated with transient fMRI-BOLD responses to smoking cues. Psychopharmacology 194, 433–441 (2007). https://doi.org/10.1007/s00213-007-0860-6

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  • DOI: https://doi.org/10.1007/s00213-007-0860-6

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