DAT genotype modulates brain and behavioral responses elicited by cigarette cues

Area of Science:

• Neuroscience
• Genetics
• Addiction Research

Background:

• Individual variability exists in brain and subjective responses to smoking cues.
• Dopamine (DA) transmission, influenced by genetic variations like the DAT gene polymorphism, is critical for reward processing.

Purpose of the Study:

• To investigate if the variable number of tandem repeats (VNTRs) polymorphism in the dopamine transporter (DAT) gene (SLC6A3) influences neural and behavioral responses to smoking cues.
• To determine if carrying the 9-repeat allele of the DAT gene enhances brain and behavioral responses.

Main Methods:

• Perfusion fMRI was used to acquire brain images in 19 smokers genotyped for the 40 bp VNTR polymorphism in the SLC6A3 gene during cue exposure.
• Brain responses to smoking versus non-smoking cues were compared between individuals with the 9-repeat allele and those homozygous for the 10-repeat allele (10/10-repeats).

Main Results:

• Smokers with the 9-repeat allele exhibited greater activation in the ventral striatal/pallidal/orbitofrontal cortex (VS/VP/OFC) in response to smoking cues compared to 10/10-repeat smokers.
• Activity increased in the VS/VP/OFC for 9-repeat carriers and decreased for 10/10-repeat carriers (p<0.001).
• Strong correlations between brain activity and craving were observed in 10/10-repeat carriers in multiple brain regions (r(2)=0.79-0.86, p<0.001), but not in 9-repeat carriers.

Conclusions:

• Genetic variation in the DAT gene significantly contributes to individual differences in neural and behavioral responses to smoking cues.
• The 9-repeat allele of the DAT gene is associated with enhanced neural responses to smoking cues, suggesting a genetic predisposition to cue-elicited activation.