Differential neural response to alcohol priming and alcohol taste cues is associated with DRD4 VNTR and OPRM1 genotypes.
BACKGROUND
Studies suggest that polymorphisms in the D4 dopamine receptor (DRD4) and opioid receptor, mu 1 (OPRM1) genes are involved in differential response to the effects of alcohol and to alcohol cues. However, to date, the mechanisms that underlie these differences remain largely unknown.


METHODS
Using functional magnetic resonance imaging, hemodynamic response in mesocorticolimbic structures after exposure to alcohol tastes was contrasted with a control taste and compared between DRD4 variable number of tandem repeats (VNTR) genotypes and OPRM1 A118G genotypes. Additionally, the effects of a priming dose of alcohol on this response were examined.


RESULTS
The results indicated that DRD4 VNTR >7 repeat individuals (DRD4.L) had significantly greater response to alcohol cues in the orbitofrontal cortex, anterior cingulate gyrus, and striatum compared with individuals with <7 repeats (DRD4.S) prior to a priming dose of alcohol (p < 0.05), but not after a priming dose. In the OPRM1 comparisons, results showed that individuals with at least 1 copy of the OPRM1 + 118 G allele had greater hemodynamic response in mesocorticolimbic areas both before and after priming compared with those who were homozygous for the OPRM1 + 118 A allele. For the DRD4.L and OPRM1 + 118 G groups, brain response in the striatum was highly correlated with measures of alcohol use and behavior such that greater activity corresponded with greater frequency and quantity of alcohol use.


CONCLUSIONS
The DRD4 VNTR and OPRM1 A118G polymorphisms are associated with functional neural changes in mesocorticolimbic structures after exposure to alcohol cues. This provides evidence for the contributions of the DRD4 and OPRM1 genes in modulating neural activity in structures that are involved in the motivation to drink.
Department of Psychology, University of Colorado at Boulder, Boulder, Colorado, USA. ffilbey@mrn.org
Francesca M
FM
Filbey
Lara
L
Ray
Andrew
A
Smolen
Eric D
ED
Claus
Amy
A
Audette
Kent E
KE
Hutchison
D000328:Adult; D000428:Alcohol Drinking / Q000235:genetics / Q000503:physiopathology*; D000434:Alcoholic Beverages; D001921:Brain / Q000503:physiopathology*; D005260:Female; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D018598:Minisatellite Repeats; D010100:Oxygen / Q000097:blood; D020641:Polymorphism, Single Nucleotide; D050638:Receptors, Dopamine D4 / Q000235:genetics*; D017450:Receptors, Opioid, mu / Q000235:genetics*; D013649:Taste
C493599:DRD4 protein, human; C485764:OPRM1 protein, human; D017450:Receptors, Opioid, mu; D050638:Receptors, Dopamine D4; D010100:Oxygen