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.

项目概要/摘要主要研究内容4 酒精是美国青少年最广泛使用的物质之一，经常酗酒在近三分之二的未成年饮酒者中，酗酒和酗酒的比例很高。令人震惊的是，即使是偶尔酗酒的青少年也更有可能表现出酗酒年轻人主要在社交场合饮酒，尽管这种背景特异性——更不用说对社会后果敏感度的性别差异——已经使用青春期大鼠模型，我们发现了显着的性别差异。乙醇导致青少年高社交饮酒的前兆和影响。男性饮酒与高社交活动和对社交便利的敏感性增强有关乙醇的影响，而在青春期女性中，社交饮酒水平较高与酒精浓度升高有关社交焦虑和对乙醇社交抗焦虑作用的敏感性增强。旨在分别确定负责高社交活动和敏感度的大脑区域与高度社交焦虑和相关区域相比，酒精在青春期男性中引起的社交促进作用增强女性对乙醇的社交抗焦虑作用的敏感性。具有高社交饮酒表型的男性和女性的差异激活将使用以下方法确定然后将使用 Daun02 程序选择性地使用转基因 cFos-LacZ 大鼠和 c-Fos 的 X-Gal 染色。使特定目标区域中的神经元失活，这些神经元仅由社会刺激激活或在与急性乙醇结合，并确定这种失活对随后社交饮酒的影响我们预计，在男性和女性的高社交饮酒者中，社交活动会激活神经系统的失活。在社交活跃度较高的男性中，单独或与急性乙醇相互作用会减弱社交饮酒在这些动物中，神经系统的失活在高度社交焦虑的青少年中被激活鉴于大脑的重要性，社交刺激会减少这些女性的社交饮酒。加压素/催产素肽系统在调节社会行为和社交焦虑中的作用，我们还将测试假设男性大量社交饮酒与大脑加压素 V1a 过度活跃有关受体，而大脑催产素系统的功能性低下会导致社交饮酒过多这些假设将通过神经药理学和蛋白质评估进行测试。催产素和加压素的水平及其在与性别相关的大脑区域中的受体该提案中概述的工作将是第一个检查神经系统的工作。导致前体中明显的性别差异的因素导致高社交饮酒率青少年，对于制定新的、针对性别的早期预防和干预战略至关重要青春期大量饮酒。