CRF NEURAL CIRCUITS OF BINGE DRINKING

CRF 酗酒的神经回路

• 批准号: 10705320
• 负责人: DENNIS R. SPARTA
• 金额: $ 35.41万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-12 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10705320
• 关键词: Accounting; Acute; Address; Alcohol consumption; Alcoholism; Amygdaloid structure; Area; Behavior; Behavioral; Brain; Brain region; Cell Nucleus; Corticotropin-Releasing Hormone; Coupled; Data; Detection; Disease; Dopamine; Electrophysiology (science); Etiology; Gene Targeting; Health; Heavy Drinking; Humpback Dolphins; Individual; Light; Maintenance; Mediating; Mus; Nature; Neuronal Plasticity; Neurons; Neuropeptides; Nucleus Accumbens; Output; Pathway interactions; Peripheral; Pharmacogenetics; Pharmacological Treatment; Physiological; Public Health; Recording of previous events; Research; Rewards; Role; Signal Transduction; Site; Slice; Societies; Stress; Structure; Structure of terminal stria nuclei of preoptic region; Synapses; Testing; United States; Ventral Tegmental Area; alcohol behavior; alcohol exposure; alcohol misuse; alcoholism therapy; antagonist; binge drinking; biological adaptation to stress; brain reward regions; cost; dopaminergic neuron; experimental study; gamma-Aminobutyric Acid; in vivo; neural circuit; neurobiological mechanism; novel; optogenetics; patch clamp; pharmacologic; preventable death; recruit; therapeutic target; therapeutically effective

Project Summary/Abstract Binge alcohol consumption is a severe public health problem and is the third leading cause of preventable death in the USA (Hingson et al., 2005; 2007). Defining the neural circuitry that modulates excessive binge alcohol intake is essential for developing effective therapeutics to treat this disease. Corticotropin releasing factor (CRF) is an important neuropeptide, in regards to binge alcohol consumption as peripheral and site- specific administrations of CRF antagonists can reduce excessive ethanol intake (Sparta et al., 2008; 2009; 2013). While CRF is found throughout the brain, the extended amygdala consisting of the central nucleus of the amygdala (CeA) and bed nucleus of the stria terminalis (BNST) CRF projections the to ventral tegmental area (VTA) remain a particularly interesting candidate targets for CRF’s modulation of binge drinking, since these structures provide direct connections from stress to reward brain regions I hypothesize that binge alcohol exposure leads to an increase of extended amygdalar CRF neuronal drive onto VTA GABA neurons. Specifically, I hypothesize that the CRF CeA to VTA projection is recruited during repeated binge drinking sessions, whereas the CRF BNST to VTA pathway is involved with the initiation of binge drinking. To test these hypotheses, I will utilize optogenetics, in vivo electrophysiology, ex vivo patch clamp, and behavior. Taken together, this proposal will provide a thorough characterization of both the CeA-and BNST-VTA CRF neural circuits after binge alcohol intake and may identify possible pharmacological targets for the treatment of alcoholism.

项目总结/文摘