Real-Time Accumbal Dopamine Signaling and Ethanol Drinking Behavior

描述(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增强和刺激作用，但对多巴胺释放在饮酒行为中的作用知之甚少。拟议的实验将确定伏隔多巴胺信号的初始测量是否与饮酒增加有关，或者更确切地说，是否与多巴胺能神经元的适应性变化有关 与获得可操作的乙醇自我给药相关的传播，对酒精饮用措施最具预测性。此外，我们将使用光遗传学方法来测试特定的多巴胺释放模式在调节食欲和消耗性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谷氨酸能投射如何影响伏隔多巴胺信号和可操作性乙醇自身给药。在本项目结束时，我们将确定增加或抑制酒精摄入量的多巴胺释放模式和大脑区域。这种促成酒精消费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。

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.