Main Research Component 4: Sex-specific neural contributors to high social drinking in adolescence

主要研究部分 4：导致青春期社交饮酒频繁的性别特异性神经因素

基本信息

批准号：
10006495
负责人：
LINDA PATIA SPEAR
金额：
$ 31.28万
依托单位：
STATE UNIVERSITY OF NY,BINGHAMTON
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-01 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10006495
关键词：
Acute Address Adolescence Adolescent Adult Affect Agonist Alcohol consumption Alcohol or Other Drugs use Alcohols American Animals Anti-Anxiety Agents Anxiety Argipressin Attenuated Brain Brain region Consumption Development Ethanol Event Exhibits FOS gene Female Female Adolescents Heavy Drinking Human Hyperactive behavior Individual Differences Ingestion Injections Intake LacZ Genes Life Male Adolescents Modeling Neurons Oxytocin Pattern Peptides Phenotype Play Preventive Intervention Procedures Proteins Rattus Regulation Research Rodent Role Sex Differences Social Behavior Social Environment Social Facilitation Social Interaction Specific qualifier value Specificity Stains Stimulus System Techniques Testing Transgenic Organisms V1a vasopressin receptor Vasopressins Vasotocin Work adverse outcome age difference alcohol effect alcohol exposure alcohol research alcohol sensitivity alcohol use disorder anxiety-like behavior anxious base binge drinking design drinking ethanol-induced social facilitation fighting indexing male receptor recruit relating to nervous system sex social social anxiety social situation underage drinking

项目摘要

PROJECT SUMMARY/ABSTRACT MAIN RESEARCH COMPONENT 4 Alcohol is one of the most widely used substances by American adolescents, with binge and heavy drinking evident in almost two thirds of underage current drinkers. These high rates of binge and heavy drinking are alarming, since adolescents who engage in even episodic heavy drinking are more likely to exhibit alcohol use disorders and other adverse consequences later in life. Young people predominantly drink in social situations, although this context specificity – let alone sex differences in sensitivity to social consequences – has been little investigated. Using a rat model of adolescence, we have shown pronounced qualitative sex differences in the precursors and effects of ethanol contributing to high social drinking among adolescents. High social drinking among males is associated with high social activity and enhanced sensitivity to the socially facilitating effects of ethanol, whereas in adolescent females, higher levels of social drinking are associated with elevated social anxiety and enhanced sensitivity to the socially anxiolytic effects of ethanol. The present proposal is designed to separately determine brain regions that are responsible for high social activity and sensitivity to ethanol-induced social facilitation in adolescent males, in contrast to regions related to high social anxiety and enhanced sensitivity to the socially anxiolytic effects of ethanol in females. Target brain regions that are differentially activated in males and females with high social drinking phenotypes will be determined using transgenic cFos-LacZ rats and X-Gal staining for c-Fos. The Daun02 procedure will then be used to selectively inactivate neuronal ensembles in specified target regions that were activated by the social stimulus alone or in combination with acute EtOH, and consequences of this inactivation on subsequent social drinking determined in male and female high social drinkers. We expect that inactivation of neural ensembles activated by social interactions alone or in combination with acute EtOH in high socially active males will attenuate social drinking in these animals, whereas inactivation of neuronal ensembles activated in high socially anxious adolescent females by social stimuli will diminish social drinking in these females. Given the critical importance of brain vasopressin/oxytocin peptide systems in regulation of social behavior and social anxiety, we will also test the hypothesis that high social drinking in males is associated with hyperactivity of the brain vasopressin V1a receptor, whereas functional hypoactivity of the brain oxytocin system contributes to high social drinking in adolescent females. These hypotheses will be tested neuropharmacologically and via assessment of protein levels for oxytocin and vasopressin and their receptors in the brain regions sex-specifically associated with high drinking phenotypes. The work outlined in this proposal will be among the first to examine neural contributors to the pronounced qualitative sex differences in precursors leading to high social drinking among adolescents, and are essential for creation of new, sex-specific early prevention and intervention strategies for heavy alcohol use in adolescence.

项目摘要/摘要主要研究组件4 酒精是美国青少年使用的最广泛使用的物质之一，饮酒和大量饮酒几乎三分之二的未成年人饮酒者的证据。这些狂暴和大量饮酒的比率是令人震惊的是，由于甚至参加大量饮酒的青少年更有可能展示酒精疾病和其他不利后果后期。年轻人主要在社交场合喝酒，尽管这种背景特异性 - 更不用说对社会后果的敏感性性别差异 - 已经是很少调查。使用青少年大鼠模型，我们显示出明显的定性性别差异乙醇的前体和影响有助于青少年的高度社会饮酒。高社会男性中的饮酒与高昂的社交活动和对社会支持的敏感性增强有关乙醇的影响，而在青春期女性中，更高水平的社交饮酒与升高有关社交焦虑和增强对乙醇社会抗焦虑作用的敏感性。目前的建议是旨在分别确定负责高度社交活动和敏感性的大脑区域乙醇引起的青少年男性社会设施与与高社交焦虑和高度有关的地区形成鲜明对比对乙醇在女性中对社会抗焦虑作用的敏感性增强。目标大脑区域将使用高社会饮酒表型的男性和女性差异激活 C-FOS的转基因CFOS-LACZ大鼠和X-GAL染色。然后，DAUN02过程将用于选择性在指定的目标区域中灭活神经元合奏，这些区域仅由社会刺激或在结合急性ETOH，以及这种失活对随后的社会饮酒的后果在男性和女性的社交饮酒者中。我们期望社会激活的神经合奏失活单独的互动或与高社会活跃男性中的急性ETOH结合会减弱社交饮酒在这些动物中，而在高度社会焦虑的青少年中激活的神经合奏的灭活通过社交刺激的女性将减少这些女性的社交饮酒。鉴于大脑的重要性血管加压素/催产素肽系统在调节社会行为和社交焦虑方面，我们还将测试假设男性的高社会饮酒与脑血管加压素V1A的多动症有关受体，而脑氧气系统的功能性不连续性有助于高度社交饮酒青少年女性。这些假设将在神经学上进行测试，并通过评估蛋白质氧和加压素的水平及其受体在大脑区域的性别特异性高饮酒表型。该提案中概述的工作将是最早检查中性的工作之一在前体中明显的定性性别差异的贡献者，导致社交饮酒高昂青少年，对于创建新的，针对性的早期预防和干预策略至关重要青春期大量饮酒。