HPA axis reactivity to stress in chronic cocaine users and healthy controls

长期可卡因使用者和健康对照者的 HPA 轴对压力的反应

• 批准号: 7911504
• 负责人: Jessica Margaret Richards
• 金额: $ 3.35万
• 依托单位: UNIV OF MARYLAND, COLLEGE PARK
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-01 至 2013-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7911504
• 关键词: Acute; Adrenal Glands; Alcohol or Other Drugs use; Behavioral; Biological; Chronic; Cocaine; Cocaine Dependence; Cocaine Users; Crime; Disease; Drug usage; Drug user; Economics; Functional disorder; Future; HIV; Homelessness; Hormones; Human; Hydrocortisone; Hypothalamic structure; Illicit Drugs; Individual; Intervention; Literature; Measures; Modeling; Nature; Neurobiology; Nicotine; Outcome; Participant; Pharmacological Treatment; Pituitary Gland; Prevention; Process; Psychological Stress; Public Health; Recruitment Activity; Relapse; Research Personnel; Risk; Role; Salivary; Sampling; Stress; System; Testing; Unemployment; addiction; biological adaptation to stress; cocaine use; comparison group; coping; hypothalamic-pituitary-adrenal axis; improved; interest; non-drug; non-smoking; public health relevance; response; social; stimulant addict; stressor; transmission process

DESCRIPTION (provided by applicant): Illicit drug use is a highly prevalent problem associated with a number of costly social and economic consequences including increased unemployment, homelessness, crime, and transmission of STDs including HIV. Given the costly and pervasive nature of illicit substance use, researchers have focused on mechanisms underlying substance use and relapse to identify targets for prevention and treatment. One biopsychological mechanism of interest is the biological stress response system: the hypothalamic-pituitary-adrenal (HPA) axis and its primary hormone, cortisol. Neurobiological models of addiction suggest that chronic substance use is associated with a deviation of the HPA axis from its normal state of functioning, which is hypothesized to contribute to a reduced ability to adapt or cope with additional stressors, thereby increasing one's risk of stress-induced relapse. A number of empirical studies in human cocaine and stimulant addicts have provided support for HPA dysregulation in chronic cocaine users, and findings suggest that this dysregulation is associated with deleterious substance use outcomes. However, existing studies are limited and key information regarding the true nature of HPA axis functioning in chronic cocaine users remains to be elucidated. Specifically, it is unclear to what extent previous findings have been confounded by the effects of acute nicotine exposure immediately prior to testing. Additionally, differences in stress induced HPA axis functioning between cocaine users and non-drug users remains unclear because few studies to date have included a comparison group of healthy non-drug users. A greater understanding of this biological mechanism is crucial in order to develop and examine pharmacological interventions for human cocaine users that specifically target HPA axis dysfunction. Thus, the current study aims to extend the literature in our understanding of how cocaine use is associated with a dysfunctional HPA axis response to psychological stress, separate from the effects of chronic and acute nicotine use. To do this, we will recruit non-smoking cocaine dependent individuals, and healthy, non-substance using control participants (also nonsmoking), and assess HPA axis reactivity to psychological stress in both samples, as measured by salivary cortisol concentrations. PUBLIC HEALTH RELEVANCE: Cocaine addiction is a chronically relapsing disorder that poses a significant public health risk, as it is associated with costly social and economic consequences. By isolating and examining the role of biological vulnerabilities underlying cocaine use, such as HPA axis dysfunction, researchers may better understand basic processes that may serve as targets for future behavioral and pharmacological treatments aimed to improve substance use outcomes. As such, the current study aims to replicate and extend previous studies by examining HPA axis reactivity to stress among a sample of non-smoking cocaine users and healthy (also non- smoking) non-substance users in order to better understand the relationship between chronic cocaine use and HPA axis dysfunction.

描述（由申请人提供）：非法毒品使用是一个非常普遍的问题，与许多昂贵的社会和经济后果有关，包括增加失业，无家可归，犯罪和传播疾病（包括艾滋病毒）的传播。鉴于非法物质使用的昂贵和普遍的性质，研究人员专注于使用物质使用和复发的机制，以识别预防和治疗的靶标。感兴趣的一种生物心理学机制是生物应激反应系统：下丘脑 - 垂体 - 肾上腺（HPA）轴及其主要激素皮质醇。成瘾的神经生物学模型表明，慢性物质使用与HPA轴偏离其正常功能状态有关，这可以假设有助于降低适应或应对其他压力源的能力，从而增加了应激诱发的复发的风险。人类可卡因和兴奋剂成瘾者的许多实证研究为慢性可卡因使用者的HPA失调提供了支持，发现这种失调与有害药物使用结果有关。但是，现有的研究是有限的，有关慢性可卡因使用者中HPA轴的真实性质的关键信息仍有待阐明。具体而言，目前尚不清楚以前的发现在测试前立即被急性尼古丁暴露的影响所困扰。此外，应力引起的HPA轴在可卡因用户和非药物使用者之间起作用的HPA轴的差异尚不清楚，因为迄今为止很少有研究包括一个健康的非药物使用者的比较组。对这种生物学机制的更深入的理解对于为人可卡因使用者开发和检查专门针对HPA轴功能障碍的可卡因使用者至关重要。因此，当前的研究旨在将文献扩展到我们对可卡因使用如何与功能失调的HPA轴对心理压力的反应有关的文献，这与慢性和急性尼古丁使用的影响分开。为此，我们将使用对照参与者（也非吸烟）募集非吸烟可卡因依赖性个体以及健康的非替代性，并通过唾液皮质醇浓度来评估两个样本中HPA轴对心理压力的反应性。 公共卫生相关性：可卡因成瘾是一种长期复发的疾病，构成了重大的公共卫生风险，因为它与昂贵的社会和经济后果有关。通过隔离和检查可卡因使用基础生物脆弱性的作用，例如HPA轴功能障碍，研究人员可以更好地理解基本过程，这些过程可能是未来行为和药理治疗的靶标，旨在改善药物使用结果。因此，当前的研究旨在通过检查HPA轴对不吸烟的可卡因使用者和健康（也非吸烟）非固定使用者的压力的反应性来复制和扩展先前的研究，以便更好地了解慢性可卡因使用和HPA轴功能障碍之间的关系。