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Behavioral and molecular characterization of oxytocin's effect on alcohol consumption

催产素对饮酒影响的行为和分子特征

基本信息

批准号：
10380613
负责人：
Sheena Potretzke
金额：
$ 2.38万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-04-01 至 2022-06-17
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10380613
关键词：
Abstinence Accounting Acute Address Affect Affinity Alcohol consumption Alcohols Animals Anxiety Attention Behavior Behavioral Behavioral Mechanisms Binding Birth Blood - brain barrier anatomy Brain Brain region CRISPR/Cas technology California Cells Clinical Complex Consumption Development Disulfiram Drug Design Drug usage FDA approved Fluorescence Fright Health Health Sciences Hormones Human Hypothalamic structure Immunohistochemistry Implant Individual Institutes Intake Investigation Knock-out Laboratories Lactation Lead Learning Liquid substance Literature Measurement Mediating Mediator of activation protein Memory Microtus Molecular Mus Naltrexone Neurosciences Oregon Oxytocin Oxytocin Receptor Pair Bond Patients Pattern Peripheral Persons Pharmaceutical Preparations Pharmacotherapy Placebos Polymerase Chain Reaction Prevalence Primates Process Reporting Research Research Personnel Reverse Transcription Rewards Rodent Rodent Model Role San Francisco Sex Differences Social Behavior Social Environment Social Interaction Social support Spectrometry Substance Use Disorder Surveys System Testing Time Tissues Translating Treatment Efficacy Treatment outcome Universities V1a vasopressin receptor acamprosate aged alcohol abuse therapy alcohol and other drug alcohol behavior alcohol craving alcohol use disorder antagonist design effective therapy efficacious treatment experimental study knockout animal novel prairie vole preclinical study preference radio frequency receptor receptor for advanced glycation endproducts sex social social influence

项目摘要

PROJECT SUMMARY: Despite the prevalence and devastating impact of alcohol use disorder (AUD), only three FDA approved pharmacotherapies exist and even fewer have proved efficacious. Thus, development of new pharmacotherapies is necessary. Of crucial importance in designing such therapies are the complex interactions of alcohol-related behaviors with the social environment, demonstrating the need for incorporating social paradigms in alcohol consumption studies. Our laboratory utilizes the unique Herdsman cage system to allow for precise, individualized measurements of both consumption and behavior in a truly social setting. Oxytocin (oxt), a hormone with crucial roles in a variety of social behaviors has drawn attention as a promising pharmacotherapy for AUD with its implicated role in mediating the processes associated with drug use, as well as its social effects, which may serve to bolster abstinence. Oxt has been shown to be effective in decreasing alcohol consumption in rodents and alcohol craving in humans. Our laboratory recently demonstrated robust effects of repeated oxt treatment in decreasing alcohol consumption in the prairie vole (Microtus ochrogaster) - a socially monogamous rodent species with demonstrated translational validity to humans through common mechanisms regulating social behaviors. Given the pharmacotherapeutic potential of oxt, it is essential to characterize the behavioral and molecular mechanisms of oxt's demonstrated ability to decrease alcohol consumption. We aim to characterize the behavioral mechanisms of oxt's effect using our Herdsman system to examine whether oxt's effects on alcohol consumption are direct or mediated by increased social interaction. We also seek to demonstrate, for the first time in prairie voles, expression patterns of the receptor for advanced glycation end products (RAGE) in the brain and transport of oxt across the blood brain barrier (BBB) facilitated by RAGE using a selective antagonist. Finally, we aim to identify through which receptor oxt is exerting its effect using selective Oxtr knock out (KO) prairie voles generated using CRISPR/Cas9. We aim to examine possible sex differences throughout our investigation. These experiments will explicate oxt's role in mediating the reward processes associated with drug use and social behavior, particularly within the context of alcohol, and serve to clarify whether oxt is a promising target for pharmacotherapy for AUD.

项目总结：尽管酒精使用障碍（AUD）的流行和破坏性影响，只有