Post-Traumatic Stress Disorder and Alcohol Dependence

描述（由申请人提供）：当前提案的主要目的是研究创伤后应激障碍（PTSD）对酒精依赖的影响。拟议的职业过渡奖将为申请人提供创伤后应激障碍动物模型和生化技术方面的新培训，以补充申请人在酒精中毒行为动物模型方面的经验。该奖项的培训阶段将使申请人准备在该奖项的R00阶段领导一个独立的研究项目。该奖项的R00阶段和申请人的独立研究生涯将继续专注于酒精中毒的负强化方面及其与其他精神疾病的神经重叠。暴露于创伤性应激源后，PTSD是一种长期的病理状态，其特征是焦虑和觉醒增加，感知愉悦的能力下降，以及对创伤相关刺激的泛化和回避。酒精依赖是强迫性的酒精使用，尽管有不良后果，在饮酒时失去控制，以及在没有药物的情况下产生耐受性导致戒断症状。过度饮酒可能是由于药物能够减轻令人厌恶的症状，包括由先前存在的情绪障碍（例如，创伤后应激障碍）产生的症状。据推测，表现出不适应应激反应的动物将表现出更高的酒精依赖易感性。由于创伤后应激障碍患者和酗酒者在边缘系统中表现出相似的神经失调模式，因此假设杏仁核和BNST作为创伤后应激障碍和酒精依赖重叠/叠加效应的神经界面。据推测，参与脑应激反应的神经调节剂（即促肾上腺皮质激素释放因子[CRF]、神经肽Y [NPY]和去甲肾上腺素[NE]）和这些边缘回路中普遍存在的神经调节剂在PTSD和酒精依赖中类似且加在一起失调。

DESCRIPTION (provided by applicant): The main objective of the current proposal is to examine the effects of post-traumatic stress disorder (PTSD) on alcohol dependence. The proposed career transition award will provide new training for the applicant in animal models of PTSD and in biochemical techniques that will complement the applicant's experience with behavioral animal models of alcoholism. The training phase of the award will leave the applicant prepared to lead an independent research program in the R00 phase of the award. The R00 phase of the award and the independent research career of the applicant beyond this award will continue to focus on the negative reinforcement aspects of alcoholism and their neural overlap with other psychiatric disorders. Following exposure to a traumatic stressor, PTSD is a long-term pathological state marked by increases in anxiety and arousal, decreases in the ability to perceive pleasure, and generalization and avoidance of trauma- related stimuli. Alcohol dependence is compulsive alcohol use despite adverse consequences, loss of control when taking alcohol, and development of tolerance that results in withdrawal symptoms in the absence of the drug. Excessive alcohol consumption can be driven by the ability of the drug to alleviate aversive symptoms, including those produced by a pre-existing emotional disorder (e.g., PTSD). It is hypothesized that animals that exhibit maladaptive stress responses will exhibit higher susceptibility to alcohol dependence. Because PTSD patients and alcoholics exhibit similar patterns of neural dysregulation in the limbic system, it is hypothesized that the amygdala and BNST serve as a neural interface for overlapping/additive effects of PTSD and alcohol dependence. It is hypothesized that neuromodulators involved in the brain stress response (i.e. corticotropin-releasing factor [CRF], neuropeptide Y [NPY], and norepinephrine [NE]) and ubiquitous in these limbic circuits are similarly and additively dysregulated in PTSD and alcohol dependence. PUBLIC HEALTH RELEVANCE: Individuals with pre-existing emotional disorders (e.g., PTSD) are highly vulnerable to develop alcohol dependence. This project will examine the overlapping neural mechanisms of PTSD and alcoholism that contribute to the similar behavioral dysregulation seen in the two disorders. A major goal of this project will be to pharmacologically block PTSD-induced increases in the vulnerability to develop alcohol dependence.