Real-Time Accumbal Dopamine Signaling and Ethanol Drinking Behavior

实时累积多巴胺信号和乙醇饮用行为

• 批准号: 9061504
• 负责人: Evgeny Alexander BUDYGIN
• 金额: $ 36.06万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-01 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9061504
• 关键词: Acute; Address; Affect; Alcohol abuse; Alcohol consumption; Alcohol dependence; Alcohols; Amygdaloid structure; Appetitive Behavior; Automobile Driving; Behavior; Behavioral; Blood; Brain Chemistry; Brain region; Consummatory Behavior; Consumption; Development; Dopamine; Ethanol; Extinction (Psychology); Frequencies; Genetic; Glutamates; Health; Individual Differences; Lead; Link; Maps; Measures; Medial; National Institute on Alcohol Abuse and Alcoholism; Neurobiology; Neurons; Nucleus Accumbens; Optics; Pattern; Population; Prefrontal Cortex; Procedures; Property; Rattus; Recording of previous events; Role; Scanning; Self Administration; Signal Transduction; Societies; Synapses; Techniques; Testing; Time; United States; Work; alcohol effect; alcohol seeking behavior; cost; design; drinking; drinking behavior; effective therapy; interest; neurobiological mechanism; neurochemistry; neurotransmission; neurotransmitter release; novel therapeutic intervention; optogenetics; research study; success; temporal measurement; transmission process; treatment strategy; uptake

DESCRIPTION (provided by applicant): Despite the evidence for the involvement of dopamine neurotransmission in the acute reinforcing and stimulating effects of alcohol, the role of dopamine release in alcohol drinking behavior is poorly understood. Proposed experiments will determine if initial measures of accumbal dopamine signaling are associated with increased ethanol-drinking or rather if adaptive changes in dopaminergic transmission, associated with the acquisition of operant ethanol-self administration, are most predictive of ethanol drinking measures. Moreover, we will employ optogenetic approaches to test the causal role of specific dopamine release patterns in regulating appetitive and consummatory drinking behaviors and to determine how glutamatergic projections from the basolateral amygdala and prefrontal cortex influence accumbal dopamine signaling and operant ethanol self-administration. At the conclusion of this project, we will have identified dopamine release patterns and brain regions, which increase or inhibit alcoho 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）：尽管有证据表明多巴胺神经传递参与了酒精的急性强化和刺激作用，但对多巴胺释放在饮酒行为中的作用了解甚少。 拟议的实验将确定是否初始测量的多巴胺信号与增加乙醇饮酒或更确切地说，如果适应性变化的多巴胺能神经元， 传输，与收购的操作性乙醇自我管理，是最预测的乙醇饮用措施。 此外，我们将采用光遗传学方法来测试特定多巴胺释放模式在调节食欲和饮酒行为中的因果作用，并确定基底外侧杏仁核和前额叶皮质的多巴胺能投射如何影响脑内多巴胺信号传导和操作性乙醇自我管理。 在这个项目结束时，我们将确定多巴胺释放模式和大脑区域，增加或抑制酒精消费。 这种有助于酒精消费的微电路的功能映射对于制定有效的酒精滥用治疗策略至关重要。