DAT genotype modulates brain and behavioral responses elicited by cigarette cues

Teresa R. Franklin, Falk W. Lohoff, Ze Wang, Nathan Sciortino, Derek Harper, Yin Li, Will Jens, Jeffrey Cruz, Kyle Kampman, Ron Ehrman, Wade Berrettini, John A. Detre, Charles P. O'Brien, Anna Rose Childress

Research output: Contribution to journalArticlepeer-review

84 Scopus citations

Abstract

We previously demonstrated differential activation of the mesocorticolimbic reward circuitry in response to cigarette cues independent of withdrawal. Despite robust effects, we noted considerable individual variability in brain and subjective responses. As dopamine (DA) is critical for reward and its predictive signals, genetically driven variation in DA transmission may account for the observed differences. Evidence suggests that a variable number of tandem repeats (VNTRs) polymorphism in the DA transporter (DAT) SLC6A3 gene may influence DA transport. Brain and behavioral responses may be enhanced in probands carrying the 9-repeat allele. To test this hypothesis, perfusion fMR images were acquired during cue exposure in 19 smokers genotyped for the 40 bp VNTR polymorphism in the SLC6A3 gene. Contrasts between groups revealed that 9-repeat (9-repeats) had a greater response to smoking (vs nonsmoking) cues than smokers homozygous for the 10-repeat allele (10/10-repeats) bilaterally in the interconnected ventral striatal/pallidal/orbitofrontal cortex regions (VS/VP/OFC). Activity was increased in 9-repeats and decreased in 10/10-repeats in the VS/VP/OFC (p<0.001 for all analyses). Brain activity and craving was strongly correlated in 10/10-repeats in these regions and others (anterior cingulate, parahippocampal gyrus, and insula; r2=0.79-0.86, p<0.001 in all regions). Alternatively, there were no significant correlations between brain and behavior in 9-repeats. There were no differences in cigarette dependence, demographics, or resting baseline neural activity between groups. These results provide evidence that genetic variation in the DAT gene contributes to the neural and behavioral responses elicited by smoking cues.

Original languageEnglish (US)
Pages (from-to)717-728
Number of pages12
JournalNeuropsychopharmacology
Volume34
Issue number3
DOIs
StatePublished - Feb 2009

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Psychiatry and Mental health

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