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

描述（由申请人提供）：酒精是一种被广泛滥用的提神药物。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尚不清楚。本研究的目的是对纹状体亚区多巴胺释放模式在大鼠饮酒行为中的作用进行首次研究。我们将利用光遗传学技术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在纹状体（背纹状体，伏隔核）非常离散的亚区中，以精确的时间序列，选择性地刺激多巴胺能神经元。因此，在这些精确的大脑区域内诱发的特定多巴胺释放模式与饮酒行为之间的因果关系将得到有效探索。在本项目结束时，我们将确定DA释放模式（强直性与阶段性）和纹状体亚区增加或抑制酒精消耗。这种有助于饮酒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。

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.