Early experience and low 5-HT markers in alcohol abuse

描述（由申请人提供）：初中和高中年龄的青少年饮酒的风险很高。生活在社会群体中的非人灵长类动物为研究社会对生物行为发展的影响提供了一个很好的模型。国家酒精滥用和酒精中毒研究所（NIAAA）有兴趣鼓励具有灵长类动物发育生物学和行为学专业知识的研究人员寻求与酒精研究人员合作，以阐明青少年酒精滥用和酒精中毒的神经生物学机制。 在此，我们提交了一个生物行为发展模型的修订，重点是在年轻的社会圈养的帽子猕猴自愿饮酒的个体差异的起源。早期产妇护理的差异被认为是消耗更多乙醇的相对风险差异的基础之一。将评价孕酮能系统活性的生物标志物（CSF 5 HIAA和催乳素对芬氟拉明的反应）。受试者的选择将基于5-羟色胺转运蛋白基因启动子区的多态性，该基因可调节β-羟色胺能活性。产妇护理将通过观察社会群体饲养的猕猴早期发育期间的母婴互动来确定。我们假设，猴子在发展过程中经历质量差的母亲照顾将表现出增加的风险表达的侵略性和冲动的行为模式作为青少年。我们假设，这些行为模式将存在于猴子，自愿消耗大量的乙醇。低血清素将有一个附加效应与低质量的孕产妇护理的侵略性，冲动和酒精消费水平。我们预测，青春期猴子表现出更高的攻击性和冲动行为模式以及低血清素，将显示1）在社会条件下乙醇消耗率增加，2）响应于压力源乙醇摄入量增加，3）当社会化饲养时，乙醇消耗与攻击性增加相关的可能性更高，4）减弱催眠作用。最后，参与HPA轴在这些关系将作为一个探索性的目标进行调查。

DESCRIPTION (provided by applicant): Adolescents of middle school and high school age are at high risk for alcohol consumption. Nonhuman primates living in social groups provide an excellent model for the study of social influences on biobehavioral development in general and alcohol abuse problem more specifically. The National Institute on Alcohol Abuse and Alcoholism (NIAAA) is interested in encouraging investigators with expertise in primate developmental biology and behavior to seek collaborations with established alcohol researchers to elucidate the neurobiological mechanisms of adolescent alcohol abuse and alcoholism. Herein we submit a revision of a model of biobehavioral development that focuses on the origins of individual differences in voluntary alcohol consumption in young socially housed bonnet macaque monkeys. Differences in early maternal care are suggested as one basis for differences in relative risk for consuming higher quantities of ethanol. Biomarkers of the activity of the serotonergic system (CSF 5HIAA and the prolactin response to fenfluramine) will be evaluated. Subjects will be selected on the basis of a polymorphism in the promoter region of the serotonin transporter protein gene that modulates serotonergic activity. Maternal care will be determined through observation of mother infant interactions during early development in social group reared macaque monkeys. We hypothesize that monkeys experiencing poor quality maternal care during development will demonstrate increased risk for the expression of aggressive and impulsive behavior patterns as adolescents. We hypothesize that these behavior patterns will be present in monkeys that voluntarily consume greater quantities of ethanol. Low serotonin will have an additive effect with low quality maternal care on levels of aggression, impulsivity, and alcohol consumption. We predict that adolescent monkeys evidencing higher aggressive and impulsive behavior patterns and low serotonin will show 1) increased rates of ethanol consumption under social conditions, 2) a greater increase in ethanol intake in response to a stressor, 3) higher probability that ethanol consumption will be associated with increased aggression when housed socially, and 4) attenuated soporific effects. Finally, involvement of the HPA axis in these relationships will be investigated as an exploratory goal.