Early experience and low 5-HT markers in alcohol abuse

酒精滥用的早期经验和低 5-HT 标记物

• 批准号: 6917904
• 负责人: Mark L. Laudenslager
• 金额: $ 39.77万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-06 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6917904
• 关键词: Macaca; aggression; alcoholic beverage consumption; alcoholism /alcohol abuse; behavior prediction; behavior test; behavioral /social science research tag; cerebrospinal fluid; early experience; ethanol; genotype; high performance liquid chromatography; impulsive behavior; juvenile animal; longitudinal animal study; maternal behavior; neurochemistry; phlebotomy; polymerase chain reaction; psychological stressor; receptor expression; self medication; serotonin receptor; serotonin transporter; social group process; socioenvironment

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.

描述（由申请人提供）：中学和高中时代的青少年饮酒风险很高。居住在社会群体中的非人类灵长类动物为研究社会影响对一般的生物行为发展和酗酒问题提供了一个极好的模型。美国国家酒精滥用与酒精中毒研究所（NIAAA）有兴趣鼓励具有灵长类动物发育生物学专业知识的研究人员与知名的酒精研究人员寻求合作，以阐明青少年酒精滥用和酒精中毒的神经生物学机制。 在本文中，我们提交了一种生物行为发展模型的修订，该模型的重点是年轻社会住所的引擎盖猕猴的自愿饮酒的个体差异的起源。提出早期孕产妇护理的差异是消耗较高量乙醇的相对风险差异的基础之一。将评估血清素能系统活性的生物标志物（CSF 5HIAA和催乳素对芬氟拉明的反应）。将根据调节5-羟色胺转运蛋白基因的启动子区域的多态性选择受试者，该基因调节血清素能活性。孕产妇护理将通过在社会群体饲养的猕猴的早期发展期间观察到母婴相互作用来确定。我们假设在开发过程中经历质量较差的孕产妇护理的猴子将表现出表达侵略性和冲动行为模式作为青少年的风险。我们假设这些行为模式将存在于自愿消耗更多乙醇的猴子中。低质量的孕产妇护理对侵略性，冲动和饮酒水平的低质量护理将产生添加作用。我们预测，青少年猴子表现出更高的侵略性和冲动行为模式和低血清素的猴子会显示1）在社会条件下增加乙醇消耗率的提高，2）响应压力源的乙醇摄入量的增加，3）乙醇消耗率更高，即乙醇消耗将与社交时增加侵略性相关，以及4）摄入效果。最后，将研究HPA轴参与这些关系，以作为探索性目标。