Neuronal ensembles of compulsive alcohol drinking

强迫性饮酒的神经元群

• 批准号: 10224712
• 负责人: Olivier George
• 金额: $ 35.55万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10224712
• 关键词: Acute; Address; Alcohol consumption; Alcohol dependence; Alcohols; Amygdaloid structure; Behavior Control; Brain; Brain region; Cell Nucleus; Chronic; Corticotropin-Releasing Hormone; Development; Event; FOS gene; Heavy Drinking; Hyperalgesia; Hypothalamic structure; Immediate-Early Genes; Investigation; Knowledge; LacZ Genes; Lateral; Lead; Literature; Mediating; Methods; Motivation; Neurobiology; Neurons; Pain; Pathway interactions; Pharmacogenetics; Pharmacology; Phenotype; Population; Rattus; Role; Saccharin; Self Administration; Structure of terminal stria nuclei of preoptic region; Techniques; Testing; Time; Transgenic Organisms; Withdrawal; alcohol exposure; anxiety-like behavior; design; experimental study; improved; negative emotional state; neurobiological mechanism; neuronal circuitry; novel; optogenetics; parabrachial nucleus; prevent; recruit; tool; vapor

Project Summary/Abstract  A  key  issue  in  the  alcohol  field  is  the  lack  of  knowledge  on  the  discreet  neuronal  ensembles  that  are  responsible  for  excessive  alcohol  drinking  in  alcohol-­dependent  subjects.  This  is  a  major  obstacle  for  the  alcohol field because investigations of the neuronal ensembles that mediate excessive alcohol drinking would  provide  a  comprehensive  understanding  of  the  neuronal  circuits  that  causally  contribute  to  alcohol  dependence. The recent development of pharmacogenetic and optogenetic tools that allow selective targeting  of  specific  neuronal  ensembles  is  a  tremendous  opportunity  to  bridge  this  gap  in  the  literature.  The  central  hypothesis  of  this  proposal  is  that  activation  of  the  parabrachial  nucleus  (PBN)  and  central  nucleus  of  the  amygdala  (CeA)  during  withdrawal  is  responsible  for  the  recruitment  of  a  set  of  discreet  neuronal  ensembles  that are scattered throughout the brain and ultimately responsible for excessive drinking and the emergence of  negative emotional states in dependent rats. We obtained robust preliminary results that show that selectively  targeting these neuronal ensembles produces long-­lasting reversal of excessive alcohol drinking in dependent  rats,  identifies  a  causal  relationship  between  these  ensembles,  and  reveals  novel  neuronal  pathways  that  contribute  to  alcohol  dependence.  Specific  Aim  1  characterizes  the  role  of  the  CeA  and  PBN  withdrawal  neuronal  ensembles  in  excessive  alcohol  drinking  in  dependent  rats.  Specific  Aim  2  dissects  the  role  of  the  different  CeA  CRF  pathways  in  the  recruitment  of  the  neuronal  ensembles  and  excessive  alcohol  drinking  in  alcohol dependence. Results from these studies have the potential to have a strong and lasting impact in the  field  because  our  approach  will  improve  our  understanding  of  the  neurobiological  mechanisms  of  alcohol  dependence and identify novel neuronal populations and circuits that specifically control behaviors associated  with alcohol dependence.

项目总结/文摘