Metabolic control of cue reactivity during alcohol withdrawal

戒酒期间线索反应的代谢控制

• 批准号: 10605564
• 负责人: Julia Katherine Brynildsen
• 金额: $ 7.17万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-12-01 至 2025-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10605564
• 关键词: Acetates; Alcohol consumption; Alcohol dependence; Alcohol withdrawal syndrome; Alcohols; American; American diet; Amino Acids; Anterior; Automobile Driving; Behavior; Behavior Therapy; Bioenergetics; Brain; Brain region; Cessation of life; Chronic; Cognition; Cognitive; Cues; Development; Diet Modification; Dopamine; Dorsal; Drug Metabolic Detoxication; Glutamates; Glutamine; Goals; Homeostasis; Individual; Intervention; Magnetic Resonance Spectroscopy; Maintenance; Measures; Mediation; Mental disorders; Metabolic; Metabolic Control; Metabolism; Mission; Modeling; National Institute on Alcohol Abuse and Alcoholism; Neurotransmitters; Participant; Patients; Persons; Population; Relapse; Research; Rewards; Role; Scanning; Specific qualifier value; Structure; System; Testing; Time; United States; Ventral Striatum; Withdrawal; Withdrawal Symptom; alcohol craving; alcohol cue; alcohol response; alcohol use disorder; behavior measurement; brain metabolism; burden of illness; chronic alcohol ingestion; cingulate cortex; cognitive reappraisal; control theory; craving; cue reactivity; deprivation; drinking; functional MRI scan; gamma-Aminobutyric Acid; glucose metabolism; insight; ketogenic diet; ketogentic; mind control; multimodal data; neural circuit; neuromechanism; novel therapeutic intervention; personalized medicine; premature; relating to nervous system; response; therapeutic development; tool

PROJECT SUMMARY Alcohol use disorder (AUD) is one of the most prevalent psychiatric disorders in the United States. Chronic alcohol consumption in individuals with AUD is associated with lowered glucose metabolism and increased acetate metabolism in the brain. Following abrupt cessation of alcohol consumption, sudden decreases in acetate may cause the brain to become “energy-deprived”, which could induce heightened craving and symptoms of withdrawal. The main goal of this proposal is to test the hypothesis that energy deprivation during withdrawal contributes to alcohol craving by influencing reward-encoding neural circuitry. Analyses for Specific Aim 1 will focus on defining the impact of altered brain metabolism in the dorsal anterior cingulate cortex (dACC) on its connectivity with the ventral striatum (VS) and on specifying the role of connectivity between the dACC and VS in facilitating whole-brain transitions to alcohol cue-induced neural activity states. Analyses for Specific Aim 2 will seek to define the relationship between metabolic function in the dACC, its role in driving whole-brain dynamics, and alcohol craving. Completion of this proposal will provide a framework for predicting the impact of metabolic interventions on brain state and craving, which will aid the development of therapeutic approaches for AUD.

项目摘要 酒精使用障碍（AUD）是美国最常见的精神疾病之一。慢性 在患有AUD的个体中，饮酒与葡萄糖代谢降低和葡萄糖代谢增加有关。 大脑中的醋酸盐代谢突然停止饮酒后， 醋酸盐可能会导致大脑变得“能量匮乏”，这可能会引起强烈的渴望， 戒断症状。这项提议的主要目标是检验一个假设，即在 戒断通过影响奖赏编码神经回路而促成酒精渴望。具体分析 目的1将集中于定义背侧前扣带皮层脑代谢改变的影响 （dACC）与腹侧纹状体（VS）的连通性，以及在指定 dACC和VS促进全脑向酒精线索诱导的神经活动状态的过渡。的分析 具体目标2将寻求定义dACC中的代谢功能、其在驾驶中的作用 全脑动力学和酒精渴望完成这项建议将提供一个框架， 代谢干预对大脑状态和渴望的影响，这将有助于治疗的发展。 接近AUD。