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. 项目概要/摘要 创伤后应激障碍 (PTSD) 和酒精使用障碍 (AUD) 是最常见的两种 精神疾病并且高度共病。由于缺乏资源而造成的社会和经济负担 对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 合并症的病理生理学基础。目前的证据表明 PTSD 和 AUD 的神经回路显着重叠，其中包括行为控制功能失调 前额皮质（PFC）。因此，调节行为的前额叶介导的认知过程的改变可能 导致疾病的高合并症。发病年龄之间有很强的相关性 青春期期间的饮酒情况以及晚年患上 AUD 的可能性。另外，青春期是 持续发展的关键时期，并且越来越多的证据表明，酗酒 青春期会对大脑和行为产生长期影响。考虑到患病率较高 青少年酗酒，因此令人惊讶的是很少有研究关注其影响 一个人在成年后应对创伤性应激事件的能力。本研究的总体假设 建议是，有青少年酗酒史并经历过创伤性应激事件的成年人 压力恢复能力降低，并且患 PTSD 和 AUD 的风险显着升高。这个实验 方法利用了由青少年间歇性重复循环组成的暴饮乙醇模型 通过吸入蒸气和单次长时间应激 (SPS) 程序进行乙醇 (AIE) 暴露，该程序被认为 模拟人类创伤性应激事件。在成年早期暴露于 AIE 和 SPS 后，大鼠将被 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：目标 1 将检验以下假设：暴露于 AIE-SPS 会导致 恐惧相关行为的药理学可逆改变。目标 2 将检验以下假设：暴露于 AIE-SPS 增加了因暴露于条件恐惧而诱发的饮酒量和复发样行为 提示。目标 3 将检验以下假设：AIE-SPS 引起的恐惧行为的改变反映了恐惧行为的改变 边缘前和边缘下与恐惧神经回路核心区域的沟通。这些小说的发现 创新研究将显着增进我们对行为缺陷和神经缺陷的理解 AUD 和 PTSD 之间复杂相互作用的潜在机制，以及是否有青少年病史 酗酒可能是一种预先存在的风险因素，不仅会增加患上创伤后应激障碍 (PTSD) 的风险 与创伤事件有关，也与澳元有关。