Prelimbic somatostatin peptide signaling in binge ethanol consumption

暴饮暴食中的边缘前生长抑素肽信号传导

• 批准号: 10610897
• 负责人: Nicole Ashley Crowley
• 金额: $ 31.67万
• 依托单位: PENNSYLVANIA STATE UNIVERSITY, THE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-20 至 2027-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10610897
• 关键词: Alcohol consumption; Alcohols; Animals; Anti-Anxiety Agents; Bathing; Behavior; Behavioral; Bilateral; Brain Diseases; Brain region; Calcium Signaling; Cannulations; Cessation of life; Chronic; Complement; Complex; Criminal Justice; Data; Disease; Drug Targeting; Electrophysiology (science); Fiber; Funding; Genetic; Goals; Health; Healthcare; Heavy Drinking; Literature; Maps; Mental disorders; Methods; Mood Disorders; National Institute on Alcohol Abuse and Alcoholism; Neurobiology; Neurons; Neuropeptides; Nucleus Accumbens; Octreotide; Output; Pathway interactions; Pattern; Peptide Signal Sequences; Peptides; Photometry; Play; Population; Prevalence; Prevention; Public Health; Relapse; Role; Signal Transduction; Site; Social Work; Somatostatin; Somatostatin Receptor; Structure of terminal stria nuclei of preoptic region; System; Technology; Therapeutic; Work; alcohol exposure; alcohol misuse; alcohol use disorder; anxiety-like behavior; anxiety-related behavior; behavioral phenotyping; binge drinking; brain cell; cell type; cost; depressive symptoms; drinking behavior; effective therapy; experimental study; genetic manipulation; hippocampal pyramidal neuron; in vivo; insight; neuropsychiatric disorder; new therapeutic target; optogenetics; prevent; reduced alcohol use; resilience; sex; societal costs; somatostatin analog; substance misuse; targeted treatment; therapeutic candidate; therapeutic target; timeline; transmission process

Project Summary Alcohol Use Disorder (AUD) is a complex psychiatric disorder with large societal and personal strain, involving many brain regions and cell types. Few effective treatments exist that specifically target the prevention of binge drinking. Understanding the underlying neurobiology of binge drinking is essential for preventing and treating this major public health problem. Ongoing work in our lab seeks to understand how somatostatin (SST) expressing GABAergic neurons in the prelimbic (PL) cortex, which have long been implicated in other neuropsychiatric disorders as an anti-depressive, resilience-conferring population of peptidergic neurons, may function as a therapeutic target for AUD. The overarching goal of this proposal is to understand how SST peptide signaling contributes to PL circuitry function, and how these pathways are modulated by binge alcohol consumption. Using a combination of electrophysiology, circuit mapping, fiber photometry, and behavior, we will explore three complementary but non-overlapping aims: we will demonstrate how SST modulates prelimbic pyramidal neurons, the specific outputs modulated by SST, and the overall behavioral phenotype of SST administration to the PL cortex. We will conduct these experiments during control conditions and in the context of binge drinking. Taken together, these experiments will determine the overall role of SST peptide effects on pathway-specific circuits of the PL cortex. In addition, we will establish the in vivo effects of SST peptide on alcohol consumption and anxiety-like behaviors, providing an overall mechanistic and functional characterization of SST in the PL cortex. These results will build upon our previous findings to elucidate the precise role of the SST peptide. Importantly, we expect these results to have the potential to inform new treatment targets for AUD.

项目概要 酒精使用障碍 (AUD) 是一种复杂的精神疾病，具有巨大的社会和个人压力，涉及 许多大脑区域和细胞类型。很少有专门针对预防暴饮暴食的有效治疗方法 喝。了解酗酒的潜在神经生物学对于预防和治疗至关重要 这一重大公共卫生问题。我们实验室正在进行的工作旨在了解生长抑素 (SST) 在前边缘 (PL) 皮质中表达 GABA 能神经元，这些神经元长期以来一直与其他 神经精神疾病作为一种抗抑郁、赋予恢复能力的肽能神经元群体，可能 作为 AUD 的治疗靶点。该提案的总体目标是了解如何 SST 肽信号传导有助于 PL 电路功能，以及这些通路如何发挥作用 受酗酒调节。结合电生理学、电路映射、 光纤光度测定和行为，我们将探索三个互补但不重叠的目标：我们将 演示 SST 如何调节前缘锥体神经元、SST 调节的特定输出以及 SST 给予 PL 皮层的总体行为表型。我们将在期间进行这些实验 控制条件和酗酒的情况。 总而言之，这些实验将确定 SST 肽对途径特异性影响的总体作用 PL 皮层的电路。此外，我们将确定 SST 肽对饮酒的体内影响 和焦虑样行为，提供 PL 中 SST 的整体机制和功能特征 皮质。这些结果将建立在我们之前的发现的基础上，以阐明 SST 肽的精确作用。 重要的是，我们预计这些结果有可能为 AUD 的新治疗目标提供信息。