Filbey Francesca M, Ray Lara, Smolen Andrew, Claus Eric D, Audette Amy, Hutchison Kent E
Department of Psychology, University of Colorado at Boulder, Boulder, Colorado, USA.
Alcohol Clin Exp Res. 2008 Jul;32(7):1113-23. doi: 10.1111/j.1530-0277.2008.00692.x.
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.
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.
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.
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.
研究表明，多巴胺D4受体（DRD4）基因和阿片受体μ1（OPRM1）基因的多态性与酒精作用及酒精线索的差异反应有关。然而，迄今为止，这些差异背后的机制仍 largely 未知。
使用功能磁共振成像，将接触酒精味道后中脑边缘叶结构的血流动力学反应与对照味道进行对比，并在DRD4可变串联重复序列（VNTR）基因型和OPRM1 A118G基因型之间进行比较。此外，还研究了预剂量酒精对这种反应的影响。
结果表明，在预剂量酒精之前（p < 0.05），与重复次数 < 7次的个体（DRD4.S）相比，DRD4 VNTR > 7次重复的个体（DRD4.L）在眶额皮质、前扣带回和纹状体对酒精线索的反应明显更强，但在预剂量酒精之后则不然。在OPRM1的比较中，结果显示，与OPRM1 + 118 A等位基因纯合子相比，至少有1个OPRM1 + 118 G等位基因拷贝的个体在预激发前后中脑边缘叶区域的血流动力学反应更强。对于DRD4.L和OPRM1 + 118 G组，纹状体中的脑反应与酒精使用和行为的测量高度相关，即活动越强，酒精使用的频率和量越大。
DRD4 VNTR和OPRM1 A118G多态性与接触酒精线索后中脑边缘叶结构的功能性神经变化有关。这为DRD4和OPRM1基因在调节与饮酒动机相关结构中的神经活动方面的作用提供了证据。
