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

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所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知之甚少。本研究的目的是进行第一次检查生理多巴胺释放模式的作用，从定义的纹状体亚区的饮酒行为在大鼠。我们将使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选择性地刺激多巴胺能神经元，在一个精确的时间序列，在非常离散的子区域的纹状体（背侧纹状体，核神经元）。因此，特定的多巴胺释放模式之间的因果关系，在这些精确的大脑区域内诱导，饮酒行为将被有效地探索。在这个项目的结论，我们将确定DA释放模式（紧张性与阶段性）和纹状体亚区，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。 公共卫生相关性：拟议的工作将汇集行为和电化学技术沿着遗传和光学方法，以解决与酒精成瘾的神经化学机制有关的问题。这项研究的结果可能会导致新的治疗策略，以抑制饮酒的兴趣。

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. PUBLIC HEALTH RELEVANCE: The proposed work will bring together behavioral and electrochemical techniques along with genetic and optical approaches to address issues related to neurochemical mechanisms of alcohol addiction. The results of this study may potentially lead to new therapeutic strategies to dampen interest in alcohol drinking.