Early experience and low 5-HT markers in alcohol abuse

说明(申请人提供)：初中和高中年龄的青少年是饮酒的高危人群。生活在社会群体中的非人灵长类动物为研究社会对一般生物行为发育的影响以及更具体地说酒精滥用问题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发育生物学和行为专业知识的研究人员寻求与知名酒精研究人员合作，以阐明青少年酒精滥用和酒精中毒的神经生物学机制。 在这里，我们提交了一个生物行为发展模型的修订版，该模型关注于在社交场所饲养的幼年帽子猕猴自愿饮酒的个体差异的根源。早期产妇护理的差异被认为是消耗更高剂量乙醇的相对风险差异的一个基础。将评估5-羟色胺能系统活性的生物标志物(脑脊液5HIAA和催乳素对芬氟拉明的反应)。受试者将根据调节5-羟色胺能活性的5-羟色胺转运蛋白基因启动子区域的多态进行选择。母婴护理将通过观察社会群体饲养的猕猴在早期发育过程中的母婴互动来确定。我们假设，在发育过程中经历低质量母爱的猴子，在青少年时期表现出攻击性和冲动行为模式的风险会增加。我们假设，这些行为模式将出现在自愿消费更多乙醇的猴子身上。低水平的5-羟色胺与低质量的母爱会对攻击性、冲动和饮酒水平产生相加的影响。我们预测，表现出更高的攻击性和冲动行为模式以及较低的5-羟色胺的青春期猴子将表现出1)社交条件下酒精消耗率增加，2)对应激源的酒精摄入量增加，3)在社交场所饮酒与攻击性增加相关的可能性更高，以及4)安眠药效果减弱。最后，HPA轴在这些关系中的参与将作为一个探索性目标进行调查。

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.