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

• 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
• 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

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（PTSD）、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。