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Sex-specific effects of infant trauma on adult alcohol drinking: Role of amygdala intercalated neurons

婴儿创伤对成人饮酒的性别特异性影响：杏仁核嵌入神经元的作用

基本信息

批准号：
10491282
负责人：
Anna Kay Radke
金额：
$ 16.93万
依托单位：
MIAMI UNIVERSITY OXFORD
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：
2021-09-20 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10491282
关键词：
Adult Affect Alcohol consumption Alcohols Amygdaloid structure Animals Automobile Driving Behavior Behavioral Model Bioinformatics Cell Nucleus Cells Clinical Coupled Data Development Disease Exposure to Extinction (Psychology)FOXP2 gene Female Foundations Fright Gene Expression Genetic Genomics Impairment Individual Infant Intercalated Cell Interneurons Knowledge Learning Measures Mediating Modeling Molecular Target Mus National Institute on Alcohol Abuse and Alcoholism Neurons Patients Pattern Pharmacotherapy Post-Traumatic Stress Disorders Protocols documentation Publishing Rattus Receptor Gene Recording of previous events Regulation Research Research Personnel Resistance Reverse Transcriptase Polymerase Chain Reaction Rodent Role Series Stress Testing Time Trauma Universities Up-Regulation Viral Viral Vector Water Work alcohol comorbidity alcohol exposure alcohol use disorder comorbidity conditioned fear designer receptors exclusively activated by designer drugs drinking drinking behavior early life adversity early life stress experience experimental study functional genomics innovation mRNA Expression male mouse model mu opioid receptors novel pediatric trauma postnatal pre-clinical research preference receptor receptor expression relating to nervous system sex stressor transcriptome sequencing trauma exposure traumatic stress whole genome

项目摘要

Project Summary Childhood trauma confers vulnerability to comorbid PTSD/AUD, particularly in female patients. Because the neural substrates mediating vulnerability to PTSD and AUD may be similar, elucidating these common mechanisms may provide the foundation for novel treatment options for both. Infant trauma is a powerful, construct-valid model of PTSD and AUD. Trauma-exposed animals show potentiated fear learning, resistance to extinction, and increased alcohol drinking as adults and there is an enhanced vulnerability to these effects in females. This proposal explores the novel hypothesis that infant trauma produces enduring upregulation in MOR expression in amygdala intercalated neurons, ultimately disinhibiting neurons of the central amygdala. Our experiments will test this hypothesis through completion of three primary specific aims. In male and female mice, we will 1) determine whether MOR mRNA expression is increased in amygdala intercalated neurons following infant trauma 2) identify novel molecular targets in the ITC that are regulated by stress and alcohol, and 3) demonstrate a causal role for intercalated cells MORs in mediating the effects of infant trauma on alcohol drinking. Infant trauma will be modeled by delivering 15 footshocks on postnatal day 17. Alcohol drinking will be assessed in a two-bottle choice, drinking in the dark paradigm. Collectively, completion of these aims will provide support for a mechanism by which early life adversity may increase sensitivity to stressors and increase drinking in adulthood. Our work will also further validate a model of traumatic stress and sex- dependent effects on alcohol drinking.

项目总结