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The Role of Amygdala Outputs in Stress-Induced Escalation of Alcohol Drinking

杏仁核输出在压力引起的饮酒增加中的作用

基本信息

批准号：
9760177
负责人：
Marcus Matthias Weera
金额：
$ 6.16万
依托单位：
LSU HEALTH SCIENCES CENTER
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-08-14 至 2021-02-13
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9760177
关键词：
Affect Alcohol consumption Alcohols American Amygdaloid structure Anatomy Attenuated Behavior Biological Brain CRF receptor type 1 Cells Cessation of life Comorbidity Corticotropin-Releasing Hormone Development Disease Engineering Exposure to Female Funding General Population Goals Human Hypothalamic structure Immunohistochemistry Incidence Individual Individual Differences Lateral Mediating Mediator of activation protein Modeling Neurobiology Neurons Odors Outcome Output Pharmaceutical Preparations Positioning Attribute Post-Traumatic Stress Disorders Prevalence Prevention strategy Public Health Rattus Receptor Signaling Research Personnel Rewards Role Signal Transduction Stimulus Stress Techniques Testing Training Trauma Traumatic Stress Disorders Work alcohol reward alcohol use disorder combat conditioning cost design economic cost epidemiology study experimental study exposed human population indexing innovation male meetings motivated behavior nerve supply neuroadaptation receptor skill acquisition stress reactivity symptom cluster targeted treatment therapeutic target treatment strategy

项目摘要

PROJECT SUMMARY Alcohol use disorder (AUD) is a major public health problem that affects millions of Americans. Traumatic stress disorders are highly co-morbid with AUD and can contribute to the development of AUD. Rat studies in our lab have shown that traumatic (predator odor) stress produces stress-induced conditioned place avoidance and escalated alcohol drinking in a subset of stressed rats, termed Avoiders, recapitulating the individual differences in stress reactivity seen in humans. Comparisons of predator odor stress-induced neuroadaptations in Avoider and Non-Avoider rats have revealed that corticotropin-releasing factor (CRF) signaling via CRF-1 receptors (CRFR1) in the central amygdala (CeA) represents one mechanism by which predator odor stress alters behavior. However, it is not known whether stress-induced plasticity in CRF-CRFR1 signaling in CeA mediates stress-induced escalation of alcohol drinking in Avoider rats, nor is it known whether altered CRFR1 signaling in CeA mediates post-stress behavior by gating the activity of specific CeA outputs. Here, I propose to test the role of 1) CeA CRF-CRFR1 signaling, 2) CeA projections to lateral hypothalamus (LH), and 3) CeA CRFR1+ projections to LH, in stress-induced escalation of alcohol drinking and reward in Avoider rats. Our overarching hypothesis is that CeALH CRFR1+ neurons mediate traumatic stress-induced escalation of alcohol drinking and reward. I will use a combination of immunohistochemistry, chemogenetics, and anatomical techniques to test this hypothesis. In Specific Aim 1, I will test the hypothesis that Avoider rats will show greater activation of CeALH CRFR1+ neurons than Non-Avoider and Control rats after predator odor stress. In Specific Aim 2, I will test the hypotheses that 1) inhibition of CeALH CRFR1+ neurons will attenuate stress-induced escalation of alcohol drinking and alcohol reward in Avoider rats, and 2) stimulation of CeALH CRFR1 neurons will increase alcohol drinking and alcohol reward in stress-naïve rats. I will use the newly-engineered male and female CRFR1:Cre rats for all experiments. The proposed work will provide information regarding brain circuit mediators and potential drug targets for the treatment of co-morbid AUD and traumatic stress disorders. In addition, this project will provide important training to a promising young alcohol neuroscientist.

项目总结