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PNAS:酗酒祸首 找到相关基因

英国科学家表示,酗酒可能和基因有关,带有这种基因的人,酒精会刺激大脑分泌较多的多巴胺,使人感到愉快和满足。这项研究报告发表在《美国国家科学院院刊》(PNAS)。

英国伦敦大学国王学院精神病学研究所的团队先以小鼠做实验,发现缺乏RASGRF-2基因的基因改造小鼠,比较不会去找酒喝。

研究人员接着找来663名14岁少年,对他们进行脑部扫描,发现在一项预期奖励的心理测试中,带有变异的RASGRF-2基因的人,大脑腹侧纹状体较为活跃。这个区域和使人感到愉快的化学物质多巴胺分泌有关。

两年后,研究团队又分析同一批少年的饮酒行为,发现带有变异的RASGRF-2基因者,喝酒比较频繁。

主持这项研究的舒曼教授表示,虽然这不能证明这个基因导致酗酒,而且许多环境因素和其他基因也可能有关连,但这项发现有助于了解为什么有些人难以抵挡酒精的诱惑,未来或许可以藉由基因检测,预测酗酒高危险群。

了解更多:

RASGRF2 regulates alcohol-induced reinforcement by influencing mesolimbic dopamine neuron activity and dopamine release

PNAS, December 5, 2012 | doi:10.1073/pnas.1211844110

The firing of mesolimbic dopamine neurons is important for drug-induced reinforcement, although underlying genetic factors remain poorly understood. In a recent genome-wide association metaanalysis of alcohol intake, we identified a suggestive association of SNP rs26907 in the ras-specific guanine-nucleotide releasing factor 2 (RASGRF2) gene, encoding a protein that mediates Ca2+-dependent activation of the ERK pathway. We performed functional characterization of this gene in relation to alcohol-related phenotypes and mesolimbic dopamine function in both mice and adolescent humans. Ethanol intake and preference were decreased in Rasgrf2−/− mice relative to WT controls. Accordingly, ethanol-induced dopamine release in the ventral striatum was blunted in Rasgrf2−/− mice. Recording of dopamine neurons in the ventral tegmental area revealed reduced excitability in the absence of Ras-GRF2, likely because of lack of inhibition of the IA potassium current by ERK. This deficit provided an explanation for the altered dopamine release, presumably linked to impaired activation of dopamine neurons firing. Functional neuroimaging analysis of a monetary incentive–delay task in 663 adolescent boys revealed significant association of ventral striatal activity during reward anticipation with a RASGRF2 haplotype containing rs26907, the SNP associated with alcohol intake in our previous metaanalysis. This finding suggests a link between the RASGRF2 haplotype and reward sensitivity, a known risk factor for alcohol and drug addiction. Indeed, follow-up of these same boys at age 16 y revealed an association between this haplotype and number of drinking episodes. Together, these combined animal and human data indicate a role forRASGRF2 in the regulation of mesolimbic dopamine neuron activity, reward response, and alcohol use and abuse.

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