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

创伤后应激障碍（PTSD）的患病率与饮酒之间存在高度的共相关 疾病（AUD），这是一个不断增长的研究领域的兴趣。目前的动物模型已经导致了重要的 深入了解创伤后应激障碍的神经回路和分子机制。但尽管 虽然在PTSD患者中AUD的患病率，但关于其潜在的神经生物学存在知识缺口， 科摩罗。这部分是由于缺乏评估创伤后应激障碍和创伤后应激障碍共同发生的动物模型。 滥用酒精这是一个关键的话题，因为经过验证的动物模型可以导致更好的机制， 了解这些疾病的共同发生，这可能最终导致更有效的治疗 战略布局在这个应用中，我们将结合联合收割机的捕食者气味（PO）暴露模型的创伤后应激障碍与酒精自我- 给药，以模拟从创伤后应激障碍发展后出现的适应不良的饮酒模式。 创伤经历目标1的研究将集中于建立和验证创伤后应激障碍的动物模型， 酒精自我给药，沿着用于模型的截止行为标准。目标2中的研究将探讨 调节代谢型谷氨酸受体（mGluR 2/3）的II组家族的适应，因为 越来越多的证据表明PTSD和AUD中的神经元功能失调。目标3的研究将侧重于 研究涉及联合核的神经回路，联合核是丘脑中线核， 创伤后应激障碍、压力和抑郁症的神经元回路和症状特征。这些研究代表了 创新战略，以促进对酒精增加敏感性机制的理解 创伤后应激障碍时喝酒

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.