Adolescent Alcohol Abuse, Traumatic Stress, and Vulnerability to Development of PTSD

青少年酗酒、创伤性应激和易患创伤后应激障碍 (PTSD)

• 批准号: 10544336
• 负责人: L Judson Chandler
• 金额: $ 45.04万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-01-01 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10544336
• 关键词: Address; Adolescence; Adolescent; Adult; Age of Onset; Alcohol abuse; Alcohol consumption; Alcohol dependence; Alcoholism; Amygdaloid structure; Anxiety Disorders; Behavior; Behavior Control; Behavioral; Brain; Brain region; Characteristics; Communication; Complex; Cues; Data; Development; Disease; Electrophysiology (science); Ethanol; Event; Exhibits; Exposure to; Extinction; Financial Hardship; Fright; GRM5 gene; High Prevalence; Human; Individual; Inhalation; Knowledge; Learning; Life; Measures; Medial; Mediating; Mental disorders; Modeling; Neurons; Patients; Persons; Phase; Physiological; Play; Post-Traumatic Stress Disorders; Predisposition; Prefrontal Cortex; Procedures; Rattus; Recording of previous events; Research; Risk; Risk Factors; Role; Self Administration; Sex Differences; Site; Stimulus; Stress; Stress and Coping; Testing; adolescent alcohol abuse; adolescent alcohol exposure; alcohol exposure; alcohol relapse; alcohol seeking behavior; alcohol use disorder; biological adaptation to stress; clinically relevant; cognitive process; comorbidity; conditioned fear; coping; critical period; design; drinking behavior; effective therapy; emerging adult; experience; experimental study; heart rate variability; high risk; in vivo; innovation; interest; male; memory process; neural circuit; neuromechanism; neuropathology; novel; optogenetics; pharmacologic; receptor; sensor; social; stress reduction; stress resilience; traumatic event; traumatic stress; underage drinking; vapor

7. PROJECT SUMMARY/ABSTRACT Post-Traumatic Stress Disorder (PTSD) and Alcohol Use Disorder (AUD) are two of the most prevalent psychiatric conditions and are highly comorbid. The social and financial burden that results from a lack of effective treatments for these disorders is enormous. Therefore, there is a clear and urgent need to gain a greater understanding of the pathophysiological basis of PTSD and AUD comorbidity. Current evidence suggests the neurocircuitry of PTSD and AUD significantly overlap, which includes dysfunctional control of behavior by the prefrontal cortex (PFC). Thus, alterations in prefrontal mediated cognitive processes that regulate behavior may contribute to the high comorbidity of the disorders. There is a strong correlation between the age of onset of alcohol use during adolescence and the likelihood of developing an AUD later in life. In addition, adolescence is a critical period of continued development, and accumulating evidence indicates that the abuse of alcohol during adolescence can have long-term consequences on brain and behavior. Considering the high prevalence of adolescent alcohol abuse, it is therefore surprising that little research has focused on understanding its impact on an individual’s ability to cope with a traumatic stress event in adulthood. The overarching hypothesis of this proposal is that adults with a history of adolescent alcohol abuse who experience a traumatic stress event have reduced stress resiliency and are at a significantly higher risk of developing PTSD and AUD. This experimental approach takes advantage of a binge ethanol model consisting of repeated cycles of Adolescent Intermittent Ethanol (AIE) exposure by vapor inhalation and a Single Prolonged Stress (SPS) procedure that is thought to model a traumatic stress event in humans. Following AIE and SPS exposure in early adulthood, rats will then be tested for alterations in fear behavior and ethanol self-administration. The following three specific aims are designed to test the overarching hypothesis: Aim 1 will test the hypothesis that exposure to AIE-SPS results in pharmacologically reversible alterations in fear-related behaviors. Aim 2 will test the hypothesis that exposure to AIE-SPS increases alcohol consumption and relapse-like behavior induced by exposure to fear conditioned cues. Aim 3 will test the hypothesis that AIE-SPS induced alterations of fear behaviors reflect alterations in prelimbic and infralimbic communication with core regions of the fear neurocircuitry. Findings from these novel and innovative studies will significantly advance our understanding of the behavioral deficits and neural mechanisms underlying the complex interactions between AUD and PTSD, and whether a history of adolescent alcohol abuse may represent a pre-existing risk factor that increases susceptibility of developing not only PTSD associated with a traumatic event but also AUD.

7。项目摘要/摘要 创伤后应激障碍（PTSD）和酒精使用障碍（AUD）是最普遍的两个 精神病疾病，高度合并。由于缺乏 这些疾病的有效治疗是巨大的。因此，明确而迫切需要获得更大的 了解PTSD和AUD合并症的病理生理基础。当前的证据表明 PTSD和AUD的神经记录显着重叠，其中包括对行为的功能障碍控制 前额叶皮层（PFC）。那就是调节行为的前额叶介导的认知过程的改变可能 有助于疾病的高合并症。发病年龄之间存在很强的相关性 青少年期间的饮酒以及以后生命后期发展AUD的可能性。另外，青少年是 持续发展的关键时期和积累的证据表明，在 青少年可能会对大脑和行为产生长期的影响。考虑到很高的患病率 因此，青春期酗酒，因此很惊讶的是，很少的研究重点是理解其影响 关于个人在成年期应对创伤性压力事件的能力。总体假设 提案是，经历了创伤性压力事件的青春期酗酒史的成年人 降低了应力弹性，并且患有PTSD和AUD的风险明显更高。这个实验 方法利用了由青少年间歇性循环组成的暴饮暴食乙醇模型 乙醇（AIE）通过蒸气吸入和单个长时间压力（SPS）程序暴露 模拟人类的创伤性压力事件。在成年初AIE和SPS暴露后，大鼠将是 测试了恐惧行为和乙醇自我给药的改变。以下三个具体目标是 旨在检验总体假设：AIM 1将检验以下假设：暴露于AIE-SPS导致 与恐惧相关行为的药理可逆变化。 AIM 2将检验暴露于 AIE-SPS增加了暴露于恐惧条件的饮酒和类似继电器的行为 提示。 AIM 3将检验AIE-SP引起的恐惧行为改变的假设反映了改变 与恐惧神经记录的核心区域的前缘和临界交流。这些小说的发现 创新的研究将大大提高我们对行为定义和中立的理解 AUD和PTSD之间复杂相互作用的基础机制，以及青少年的历史 酒精滥用可能是现有的危险因素，不仅增加了PTSD的敏感性 与创伤事件有关，也与AUD相关联。