Characterization of alcohol self-administration following predator odor exposure: relevance to PTSD

暴露于捕食者气味后自我饮酒的特征：与 PTSD 的相关性

基本信息

批准号：
9976414
负责人：
JOYCE BESHEER
金额：
$ 48.22万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-12 至 2022-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9976414
关键词：
Agonist Alcohol consumption Alcohols Animal Model Animals Anxiety Area Behavior Behavioral Communication Control Groups Data Designer Drugs Development Disease Family Feces Female Foxes Glutamates Goals Heavy Drinking High Prevalence Hippocampus (Brain)Investigation Knowledge Lead Mental Depression Metabotropic Glutamate Receptors Methods Midline Thalamic Nuclei Modeling Molecular Neurobiology Odors Patients Pattern Pharmacology Post-Traumatic Stress Disorders Predisposition Prevalence Rattus Receptor Activation Recording of previous events Regulation Research Reuniens Thalamic Nucleus Role Self Administration Series Stress Subgroup Sucrose Symptoms Time Training Validation Water alcohol misuse alcohol reinforcement alcohol use disorder base brain circuitry comorbidity drinking effective therapy experience experimental study innovation insight interest male neural circuit neuroadaptation neurobiological mechanism receptor receptor expression traumatic stress treatment strategy

项目摘要

There is high comorbidity between the prevalence of post-traumatic stress disorder (PTSD) and alcohol use disorders (AUD) and this is a growing research area of interest. Current animal models have led to important insights into the neural circuits and molecular mechanisms involved in PTSD alone. However, despite the prevalence of AUD in patients with PTSD, there is a knowledge gap regarding the underlying neurobiology of comorbidity. This is due, in part, to the lack of animal models assessing the co-occurrence of PTSD and alcohol misuse. This is a critical topic, as validated animal models can lead to a better mechanistic understanding of the co-occurrence of these disorders, which may ultimately lead to more effective treatment strategies. In this application, we will combine a predator odor (PO) exposure model of PTSD with alcohol self- administration to model the emergence of maladaptive drinking patterns following development of PTSD from a traumatic experience. Studies in Aim 1 will focus on establishing and validating an animal model of PTSD and alcohol self-administration, along with cutoff behavioral criteria for use in the model. Studies in Aim 2 will probe adaptations in the Group II family of regulatory metabotropic glutamate receptors (mGluR2/3) as there is growing evidence for glutamatergic dysregulation in both PTSD and AUD. Studies in Aim 3 will focus on examining neural circuitry involving the nucleus reuniens, a midline thalamic nucleus, that has been emerging in the glutamatergic circuitry and symptom profile of PTSD, stress and depression. These studies represent an innovative strategy to advance understanding of mechanisms underlying susceptibility to increased alcohol drinking in PTSD.

创伤后应激障碍（PTSD）的患病率与饮酒之间存在高度共存病疾病（AUD），这是一个日益受到关注的研究领域。目前的动物模型已经产生了重要的深入了解与 PTSD 相关的神经回路和分子机制。然而，尽管尽管 AUD 在 PTSD 患者中的患病率很高，但关于 AUD 的潜在神经生物学方面存在知识差距合并症。部分原因是缺乏评估 PTSD 和 PTSD 共存的动物模型。酒精滥用。这是一个关键的话题，因为经过验证的动物模型可以带来更好的机制了解这些疾病的同时发生，这可能最终导致更有效的治疗策略。在此应用中，我们将 PTSD 的捕食者气味 (PO) 暴露模型与酒精自我管理来模拟 PTSD 发展后出现的适应不良饮酒模式创伤经历。目标 1 的研究将侧重于建立和验证 PTSD 动物模型以及酒精自我管理，以及模型中使用的截止行为标准。目标 2 的研究将探讨调节性代谢型谷氨酸受体 (mGluR2/3) II 组家族的适应性越来越多的证据表明 PTSD 和 AUD 中谷氨酸能失调。目标 3 的研究将集中于检查涉及核团聚核（中线丘脑核）的神经回路，该核团已经出现谷氨酸能回路以及创伤后应激障碍、压力和抑郁的症状特征。这些研究代表了促进对酒精增加易感性机制的理解的创新策略患有创伤后应激障碍（PTSD）时饮酒。