CONTEXT: Neuropeptide Y (NPY) counters stress and is involved in neuroadaptations that drive escalated alcohol drinking in rodents. In humans, low NPY expression predicts amygdala response and emotional reactivity. Genetic variation that affects the NPY system could moderate stress resilience and susceptibility to alcohol dependence. OBJECTIVE: To determine whether functional NPY variation influences behavioral adaptation to stress and alcohol consumption in a nonhuman primate model of early adversity (peer rearing). DESIGN: We sequenced the rhesus macaque NPY locus (rhNPY) and performed in silico analysis to identify functional variants. We performed gel shift assays using nuclear extract from testes, brain, and hypothalamus. Levels of NPY in cerebrospinal fluid were measured by radioimmunoassay, and messenger RNA levels were assessed in the amygdala using real-time polymerase chain reaction. Animals were exposed to repeated social separation stress and tested for individual differences in alcohol consumption. Animals were genotyped for -1002 T > G, and the data were analyzed using analysis of variance. SETTING: National Institutes of Health Animal Center. Subjects Ninety-six rhesus macaques. Main Outcome Measure Behavior arousal during social separation stress and ethanol consumption. RESULTS: The G allele altered binding of regulatory proteins in all nuclear extracts tested, and -1002 T > G resulted in lower levels of NPY expression in the amygdala. Macaques exposed to adversity had lower cerebrospinal fluid NPY levels and exhibited higher levels of arousal during stress, but only as a function of the G allele. We also found that stress-exposed G allele carriers consumed more alcohol and exhibited an escalation in intake over cycles of alcohol availability and deprivation. CONCLUSIONS: Our results suggest a role for NPY promoter variation in the susceptibility to alcohol use disorders and point to NPY as a candidate for examining gene x environment interactions in humans.
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机译：背景:神经肽Y (NPY)和柜台压力参与神经,开车吗在啮齿动物升级饮酒。低NPY表达杏仁核响应和预言情感上的反应。影响NPY系统可以适度的压力弹性和对酒精的易感性依赖。功能性NPY变异影响行为适应压力和饮酒非人灵长类动物模型的早期逆境(同行饲养)。NPY轨迹(rhNPY)和在计算机执行分析识别功能变体。使用核提取物凝胶转变进行化验从睾丸、大脑和下丘脑。NPY在脑脊液被衡量未及,信使RNA水平使用实时评估的杏仁核聚合酶链反应。重复社会分离压力和考验个体差异的酒精消费。G,并使用分析数据进行了分析方差。动物中心。猕猴。在社会压力和乙醇分离消费。绑定的调控蛋白核提取测试,和-1002 T > G导致低水平的杏仁核NPY的表达。猕猴暴露于逆境较低脑脊液NPY水平和展出在压力较高的兴奋,但作为一个G等位基因的功能。stress-exposed G等位基因携带者消耗更多在摄入酒精和展出升级在周期的可用性和酒精剥夺。NPY子变异的作用对酒精使用障碍的易感性和点为研究基因x NPY作为候选人在人类环境的相互作用。
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