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: 9057929
• 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/9057929
• 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; Corticotropin-Releasing Hormone; Coupled; Cues; Data; Dependovirus; Disease; Dorsal; Electrophysiology (science); Ethanol; Future; Genetic; Genetic Techniques; Goals; Health; Home environment; Implant; Intoxication; Investigation; Lesion; Locomotion; Mediating; 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; Suid Herpesvirus 1; Testing; Thalamic structure; Therapeutic; United States; Virus; alcohol availability; alcohol behavior; alcohol response; alcohol reward; alcohol seeking behavior; alcohol use disorder; designer receptors exclusively activated by designer drugs; drinking; drinking behavior; experience; gamma-Aminobutyric Acid; hindbrain; in vivo; insight; natural hypothermia; neuronal circuitry; optical fiber; optogenetics; parabrachial nucleus; preference; research study; 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具有巨大的社会和财政影响。此外，酒精是可预防死亡的第三主要原因（Mokdad等，2004）。阐明有助于酒精奖励特性的神经元电路可能会深入了解治疗酒精使用障碍的治疗机制。杏仁核（CEA）的中央核已显示在调节饮酒行为的各个方面起作用，但是，CEA是一种异质性核，其中不同的遗传定义种群可能以不同的方式对乙醇相关的行为有助于。该建议旨在评估CEA-神经素（NTS）神经元在使用尖端工具中介导乙醇中毒和自我管理中的因果作用。我将进行免疫组织化学，行为和电生理实验。特别是我将研究后脑中对副核（PBN）的投影，该区域被认为在压力和焦虑中起着重要作用。通过这项研究，我计划表明，将投射到PBN的CEA-NTS神经元因酒精和相关的提示而被激活，并介导某些奖励酒精的奖励特性。这些实验将发现可能导致酒精使用障碍的新神经元电路和机制，并允许将来的靶标治疗该病理学。