Effects of Isolation Rearing on Dopamine Release and Reuptake

隔离饲养对多巴胺释放和再摄取的影响

• 批准号: 8125883
• 负责人: Jordan Thomas Yorgason
• 金额: $ 4.18万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-15 至 2014-08-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8125883
• 关键词: Acute; Admission activity; Affect; Alcohol abuse; Alcohol consumption; Alcohol dependence; Alcoholism; Alcohols; Amygdaloid structure; Animal Housing; Animal Model; Animals; Anxiety; Area; Autoreceptors; Basic Science; Behavior; Behavioral; Brain; Chronic; Data Set; Development; Disease; Dopamine; Drug Delivery Systems; Drug abuse; Elderly; Ethanol; Event; Exhibits; Extinction (Psychology); Housing; Human; Impulsivity; Kinetics; Lead; Life; Measures; Modeling; Monitor; National Research Service Awards; Neurons; Nucleus Accumbens; Pharmaceutical Preparations; Plastics; Play; Predisposition; Presynaptic Terminals; Property; Psychological reinforcement; Public Health; Rattus; Recurrent disease; Regulation; Relative (related person); Reporting; Research; Resistance; Resolution; Risk Factors; Role; Safety; Scanning; Signal Transduction; Slice; Social isolation; Structure; Techniques; Time; United States; United States Substance Abuse and Mental Health Services Administration; addiction; alcohol effect; alcohol reinforcement; alcohol response; alcohol seeking behavior; clinically relevant; controlled release; dopamine system; dopamine transporter; dopaminergic neuron; drinking; drug of abuse; drug reward; environmental change; environmental intervention; innovation; insight; mesolimbic system; neurochemistry; neurotransmission; presynaptic; psychologic; psychostimulant; relating to nervous system; research study; response; reuptake; social; social group; tool; transmission process; uptake

DESCRIPTION (provided by applicant): Postweanling social isolation rearing produces long term changes in many behaviors, including increased locomotor novelty response, increased anxiety-like behavior, and increased ethanol consumption. In addition, isolates also show changes in dopaminergic activity, including increases in ventral tegmental dopamine neuron burst firing, increased accumbal dopamine, and increased dopamine turnover in the accumbens and amygdala. However, these previous studies are limited in that they do not reveal aspects of presynaptic terminal function. Fast scan cyclic voltammetry is a powerful tool for measuring presynaptic function due to its high temporal and spatial resolution. In the present study, we will investigate uptake rates and autoreceptor sensitivity as well as ethanol responsiveness in social isolation and group housing reared animals using voltammetry. We will be focusing on function within the nucleus accumbens and basolateral amygdala, as these areas believed to be important for ethanol's reinforcing properties. PUBLIC HEALTH RELEVANCE: The research proposed in this NRSA is significant as alcohol abuse is a major concern for public health and safety. Indeed, alcohol is reported as one of the most abused substances within the United States, representing ~40% of all admissions to drug abuse treatment facilities (SAMHSA, Treatment Episode Data Set, 2008). Because basic science research of alcohol abuse implements non-human animal models, it is important for translational purposes that these animal models somewhat reflect the disorder. For example, animal models of increased drinking may help elucidate the underlying neuronal substrates/mechanisms behind alcoholism. Rats raised in social isolation are a promising candidate for such a model. Similar to humans, socially isolated rats show increases in anxiety and impulsivity, that seemingly predict alcohol consumption levels. Dopamine's putative role in ethanol reinforcement, make it a prime candidate for studying the neural correlates of alcohol abuse. By studying the dopamine systems of these animals, we may gain important insight into underlying mechanisms that increase an animal's propensity to drink. This research is clinically relevant in that it may help direct the development of new drugs for treating alcoholism.

描述（由申请人提供）：断奶后社会隔离饲养在许多行为中产生长期变化，包括运动新奇反应增加、焦虑样行为增加和乙醇消耗增加。此外，分离物还显示多巴胺能活性的变化，包括腹侧被盖多巴胺神经元爆发放电的增加、丘脑多巴胺的增加以及丘脑和杏仁核中多巴胺周转的增加。然而，这些以前的研究是有限的，因为他们没有揭示突触前末梢功能的方面。快速扫描循环伏安法具有很高的时间和空间分辨率，是测量突触前功能的有力工具。在本研究中，我们将调查的摄取率和自身受体的敏感性，以及乙醇的反应性，在社会隔离和群体住房饲养的动物使用伏安法。我们将重点关注杏仁核和基底外侧杏仁核的功能，因为这些区域被认为对乙醇的强化特性很重要。 公共卫生相关性：本NRSA中提出的研究具有重要意义，因为酗酒是公共卫生和安全的主要问题。事实上，据报告，酒精是美国境内滥用最严重的物质之一，约占药物滥用治疗机构所有收治人数的40%（SAMHSA，治疗事件数据集，2008年）。由于酒精滥用的基础科学研究采用非人类动物模型，因此这些动物模型在某种程度上反映了这种疾病，这对于翻译目的很重要。例如，增加饮酒的动物模型可能有助于阐明酒精中毒背后的潜在神经基质/机制。在社会隔离中饲养的老鼠是这种模型的一个有希望的候选人。与人类相似，社交孤立的老鼠表现出焦虑和冲动的增加，这似乎预示着酒精消费水平。多巴胺在酒精强化中的假定作用，使其成为研究酒精滥用神经相关性的主要候选者。通过研究这些动物的多巴胺系统，我们可能会对增加动物饮酒倾向的潜在机制有重要的了解。这项研究具有临床意义，因为它可能有助于指导治疗酒精中毒的新药的开发。