Dopamine Release Patterns in Alcohol-drinking Behavior: An Optogenetic Study

饮酒行为中的多巴胺释放模式：光遗传学研究

• 批准号: 8462878
• 负责人: Evgeny Alexander BUDYGIN
• 金额: $ 16.34万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-05-01 至 2014-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8462878
• 关键词: Acute; Address; Alcohol abuse; Alcohol consumption; Alcohol dependence; Alcohols; Behavior; Behavioral; Brain region; Characteristics; Corpus striatum structure; Cues; Development; Dopamine; Dorsal; Ethanol; Feedback; Frequencies; Genetic; Goals; Intake; Lead; Light; Location; Maps; Motivation; Neurobiology; Nucleus Accumbens; Optics; Pattern; Pharmaceutical Preparations; Physiologic pulse; Physiological; Process; Rattus; Role; Scanning; Schedule; Self Administration; Signal Transduction; Substantia nigra structure; Techniques; Testing; Training; Ventral Tegmental Area; Work; alcohol behavior; alcohol effect; base; behavior test; design; dopaminergic neuron; drinking; drinking behavior; effective therapy; extracellular; interest; neurochemistry; neurotransmission; novel therapeutics; optogenetics; putamen; research study; success; treatment strategy; uptake

DESCRIPTION (provided by applicant): Alcohol is a widely abused, reinforcing drug. The success of developing effective treatments for alcohol abuse depends on a detailed understanding of the neurobiological changes involved in the development of addictive processes. Despite the evidence for the involvement of dopamine neurotransmission in the acute reinforcing and stimulating effects of alcohol, the role of dopamine release n alcohol drinking behavior is poorly understood. The goal of this study is to conduct the first examination of the role of physiological dopamine release patterns from defined striatal subregions on alcohol drinking behaviors in rats. We will selectively manipulate the pattern and location of dopamine release in the striatum of drinking rats using optogenetics. This cutting-edge technique will allow us to selectively stimulate dopaminergic neurons, in a precise temporal sequence, within very discrete subregions of the striatum (dorsal striatum, nucleus accumbens). Therefore, the causal relationships between specific dopamine release patterns, induced within these precise brain regions, and drinking behavior will be effectively explored. At the conclusion of this project, we will have identified DA release patterns (tonic versus phasic) and striatal subregions which increase or inhibit alcohol consumption. This functional mapping of the microcircuitry contributing to alcohol consumption will be critical for the developing effective treatment strategy for alcohol abuse.

描述（由申请人提供）：酒精是一种广泛滥用的强化药物。开发有效的酒精滥用治疗方法的成功取决于对成瘾过程发展中涉及的神经生物学变化的详细了解。 尽管有证据表明多巴胺神经传递参与酒精的急性强化和刺激作用，但多巴胺释放在饮酒行为中的作用仍知之甚少。本研究的目的是首次检查特定纹状体分区的生理多巴胺释放模式对大鼠饮酒行为的作用。我们将利用光遗传学选择性地操纵饮酒大鼠纹状体中多巴胺释放的模式和位置​​。这项尖端技术将使我们能够以精确的时间顺序选择性地刺激纹状体非常离散的子区域（背侧纹状体、伏隔核）内的多巴胺能神经元。因此，将有效地探索这些精确的大脑区域内诱导的特定多巴胺释放模式与饮酒行为之间的因果关系。在该项目结束时，我们将确定 DA 释放模式（强直性与阶段性）和增加或抑制酒精消耗的纹状体分区。 这种促进饮酒的微电路的功能图谱对于制定有效的酒精滥用治疗策略至关重要。

项目成果

Understanding the role α7 nicotinic receptors play in dopamine efflux in nucleus accumbens.

了解 α7 烟碱受体在伏隔核多巴胺流出中的作用。

• DOI: 10.1021/cn500126t
• 发表时间: 2014
• 期刊: ACS chemical neuroscience
• 影响因子: 5
• 作者: Maex,Reinoud;Grinevich,VladimirP;Grinevich,Valentina;Budygin,Evgeny;Bencherif,Merouane;Gutkin,Boris
• 通讯作者: Gutkin,Boris