Deconstructing the role of central nucleus of the amygdala neurotensin neurons in alcohol reward and intoxication

解构杏仁核神经降压素神经元中央核在酒精奖赏和中毒中的作用

• 批准号: 9257247
• 负责人: Zoe Anastasia McElligott
• 金额: $ 13.5万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-05-01 至 2020-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9257247
• 关键词: Abstinence; Address; Alcohol consumption; Alcoholic Intoxication; Alcohols; Amygdaloid structure; Animals; Anti-Anxiety Agents; Anxiety; Area; Attenuated; Behavior; Behavior assessment; Behavioral; Cell Nucleus; Cells; Cessation of life; Chronic; Corticotropin-Releasing Hormone; Coupled; Cues; Data; Dependovirus; Disease; Dorsal; Electrophysiology (science); Ethanol; Future; Genetic; Genetic Techniques; Goals; Home environment; Implant; Intoxication; Investigation; Lesion; Locomotion; Mediating; Medical; Motivation; Mus; Neurons; Neuropeptides; Neurotensin; Opsin; Optics; Pathology; Pathway interactions; Peptides; Play; Population; Property; Recurrent disease; Research; Rewards; Role; Sedation procedure; Self Administration; Self-Administered; Sensory; Side; Stress; Testing; Thalamic structure; Therapeutic; United States; Viral; Virus; alcohol availability; alcohol behavior; alcohol response; alcohol reward; alcohol seeking behavior; alcohol use disorder; drinking; drinking behavior; experience; experimental study; gamma-Aminobutyric Acid; hindbrain; in vivo; insight; mad itch virus; natural hypothermia; neuronal circuitry; optical fiber; optogenetics; parabrachial nucleus; preference; public health relevance; tool; treatment strategy

DESCRIPTION (provided by applicant): Alcohol use disorders have an enormous societal and fiscal impact in the United States. Moreover, alcohol is the third leading cause of preventable death (Mokdad et al., 2004). Elucidating the neuronal circuitry that contributes to the rewarding properties of alcohol may provide insight into therapeutic mechanisms for treating alcohol use disorders. The central nucleus of the amygdala (CeA) has been shown to play a role in regulating various aspects of alcohol drinking behavior, however, the CeA is a heterogeneous nucleus where different genetically defined populations may contribute to ethanol related behaviors in different ways. This proposal aims to assess the causal role of CeA-neurotensin (NTS) neurons in mediating ethanol intoxication and self-administration using cutting edge tools. I will perform immunohistochemical, behavioral and electrophysiological experiments. In particular I will investigate the projection to the parabrachial nuclei (PBN) in the hindbrain, a region that is thought to play a major role in stress and anxiety. Through this research I plan to show that CeA-NTS neurons that project to the PBN are activated in response to alcohol and associated cues and mediate some of the rewarding properties of alcohol. These experiments will uncover new neuronal circuitry and mechanisms that may contribute to alcohol use disorders and allow for future targets for the treatment of this pathology.

描述（由申请人提供）：酒精使用障碍在美国产生巨大的社会和财政影响。此外，酒精是可预防死亡的第三大原因（Mokdad 等，2004）。阐明有助于酒精有益特性的神经元回路可能有助于深入了解治疗酒精使用障碍的治疗机制。杏仁核 (CeA) 的中央核已被证明在调节饮酒行为的各个方面发挥作用，然而，CeA 是一个异质核，其中不同的基因定义的群体可能以不同的方式促进乙醇相关行为。该提案旨在使用尖端工具评估 CeA-神经降压素 (NTS) 神经元在介导乙醇中毒和自我给药中的因果作用。我将进行免疫组织化学、行为和电生理学实验。我将特别研究后脑臂旁核（PBN）的投射，该区域被认为在压力和焦虑中发挥着重要作用。通过这项研究，我计划证明投射到 PBN 的 CeA-NTS 神经元会响应酒精和相关线索而被激活，并介导酒精的一些有益特性。这些实验将揭示可能导致酒精使用障碍的新神经元回路和机制，并为治疗这种病理学提供未来的目标。