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有很高的共患率 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导致了重要的 对仅涉及创伤后应激障碍的神经回路和分子机制的洞察。然而，尽管 在创伤后应激障碍患者中AUD的患病率，关于其潜在的神经生物学方面的知识缺口 合并症。这在一定程度上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。 酗酒。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械学 了解这些疾病的共同发生情况，这最终可能导致更有效的治疗 战略。在本应用程序中，我们将结合创伤后应激障碍的捕食者气味(PO)暴露模型和酒精自身 政府对创伤后应激障碍发展后出现的适应不良饮酒模式进行建模 创伤性经历。目标1的研究将集中在建立和验证创伤后应激障碍的动物模型和 酒精自我给药，以及模型中使用的截止行为标准。AIM 2的研究将探索 第二组调节性代谢性谷氨酸受体家族(mGluR2/3)的适应性 越来越多的证据表明创伤后应激障碍和AUD患者的谷氨酸能失调。目标3的研究将集中在 检查正在出现的丘脑中线核--团结核的神经回路 在创伤后应激障碍的谷氨酸能回路和症状谱中，应激和抑郁。这些研究代表了一个 促进对酒精易感性潜在机制的理解的创新战略 在创伤后应激障碍中饮酒。

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.