Serotonin transporter gene variation is associated with alcohol sensitivity in rhesus macaques exposed to early-life stress
Serotonin transporter gene variation is associated with alcohol sensitivity in rhesus macaques exposed to early-life stress
复制标题
DOI：
10.1097/01.alc.0000067976.62827.ed
复制
发表时间：
2003-05-01
影响因子：
3.2
通讯作者：
Higley, JD
中科院分区：
文献类型：
--
作者：
Barr, CS;Newman, TK;Higley, JD
背景资料：对酒精的敏感性降低已被证明是人类酒精中毒的预测因子，5-羟色胺转运蛋白（5-HTTLPR）基因连锁多态性区域的变异与对酒精运动损伤效应的反应相关。在过量饮酒的非人灵长类动物模型中，我们已经表明，减少血清素周转与较低的初始酒精敏感性和较高的预期酒精消费量使用恒河猴。此外，我们已经证明，与母亲分开并在同龄人群体中饲养的猕猴更有可能在成年后饮酒。方法：研究5-羟色胺转运体基因型、早期养育经历和初始酒精敏感性之间的关系，在两个测试期内，在静脉内施用乙醇（雄性和雌性分别为2.2 g/kg和2.0 g/kg）后，对未接触过酒精的恒河猴（n=123）的中毒进行评级。羟色胺转运体使用聚合酶链反应随后凝胶电泳确定（rh 5-HTTLPR）基因型，并使用ANOVA和Mann-Whitney U检验分析数据。我们的分析证明了5-羟色胺转运蛋白基因变异对乙醇敏感性的影响，例如l等位基因纯合子动物对酒精的共济失调和镇静作用的敏感性降低，在校正血液乙醇浓度和出生队列后，这种影响仍然存在。当动物被隔离，根据饲养条件，5-羟色胺转运蛋白基因变异预测中毒分数之间的同行饲养animals.Conclusions：在一些人类的报告，这项研究表明，在酒精的反应减少纯合子的l rh 5-HTTLPR等位基因的动物。然而，这种基因型在l/s动物中的表型表达。是依赖环境的。
Background: Decreased sensitivity to alcohol has been demonstrated to be a predictor of alcoholism in humans, and variation in the gene-linked polymorphic region of the serotonin transporter (5-HTTLPR) is associated with the response to the motor-impairing effects of alcohol. In a nonhuman primate model of excessive alcohol intake, we have shown that decreased serotonin turnover is associated with both lower initial sensitivity to alcohol and higher prospective alcohol consumption using rhesus macaques. In addition, we have demonstrated that macaques separated from their mothers and reared in peer-only groups are more likely to consume alcohol as adults.Method: To examine the relationship between serotonin transporter genotype, early rearing experience, and initial sensitivity to alcohol, peer- and mother-reared, adolescent, alcohol-naive rhesus macaques (n=123) were rated for intoxication after intravenous administration of ethanol (2.2 g/kg and 2.0 g/kg for males and females, respectively) during two testing periods. Serotonin transporter (rh5-HTTLPR) genotype was determined using polymerase chain reaction followed by gel electrophoresis, and data were analyzed using ANOVA and the Mann-Whitney U test.Results: Our analyses demonstrate an effect of serotonin transporter gene variation on ethanol sensitivity, such that animals homozygous for the l allele exhibited decreased sensitivity to the ataxic and sedating effects of alcohol, This effect remained after correction for blood ethanol concentrations and birth cohort. When animals were segregated according to rearing condition, serotonin transporter gene variation predicted intoxication scores among peer-reared animals.Conclusions: As in some human reports, this study demonstrates a diminution in the response to alcohol in animals homozygous for the l rh5-HTTLPR allele. The phenotypic expression of this genotype in l/s animals, however. is environmentally dependent.