Role of HPA activation in opioid dependence and withdrawal

HPA 激活在阿片类药物依赖和戒断中的作用

• 批准号: 8526982
• 负责人: DAVID Richard MAGUIRE
• 金额: $ 5.22万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8526982
• 关键词: Abstinence; Acute; Adrenal Glands; Adrenal hormone preparation; Behavior; Behavioral; Body Temperature; Chronic; Corticotropin; Data; Dependence; Development; Dose; Drug abuse; Drug usage; Drug user; Exposure to; Food; Foundations; Future; Grant; Heart Rate; Hormones; Hydrocortisone; Hypothalamic structure; Individual; Injection of therapeutic agent; Journals; Laboratories; Lead; Left; Link; Macaca mulatta; Measures; Mediating; Monkeys; Morphine; Naltrexone; Neurosecretory Systems; Opiate Addiction; Opioid; Pharmaceutical Preparations; Physiological; Pituitary Gland; Play; Public Health; Relapse; Research; Research Personnel; Role; Signs and Symptoms; Staging; Structure; System; Temperature; Training; Withdrawal; career; career development; design; effective therapy; endogenous opioids; experience; hypothalamic-pituitary-adrenal axis; indexing; meetings; opioid abuse; opioid withdrawal; overdose death; post-doctoral training; programs; public health relevance; response

DESCRIPTION (provided by applicant): Opioid abuse continues to be a significant public health problem. Opioids have high abuse and dependence liability and their misuse can lead to overdose and death. Successful treatment of drug abuse is often hindered by difficulty in promoting sustained abstinence in current drug users. Many factors contribute to continued opioid abuse and the resumption of opioid use after periods of abstinence (relapse). An understanding of these factors will contribute to the development of more effective treatments. Prolonged use of opioids has been associated with significant changes in neuroendocrine function, particularly in activity of the hypothalamic- pituitary-adrenal (HPA) axis, and these changes have been linked to the emergence of withdrawal and continued drug use. Although the association between HPA activation and withdrawal has been established, it is not known exactly what roles(s) HPA activation might play. One possibility is that HPA activation serves as a trigger that elicits some manifestations of withdrawal and that withdrawal-associated effects, in turn, promote drug taking/relapse. Studies in this application will examine changes in HPA axis activity during the development of opioid dependence and withdrawal and compare changes in HPA axis activity with effects on behavioral and physiological measures. Consequently, this research will set the stage for future studies examining the role that activation of the HPA axis might serve in mediating the transition from abstinence to drug taking. Studies in Aim 1 will determine the acute effects of morphine and of naltrexone on HPA axis activity and behavioral and physiological measures. Studies in Aim 2 will examine changes that occur in behavioral, physiological, and endocrinological measures, during daily administration of morphine and following discontinuation of daily morphine treatment. Changes in HPA axis activity during different morphine treatments will be compared to behavioral and physiological measures that have been established as reliable indicators of opioid dependence and withdrawal. These studies will provide foundational set of studies on the changes in HPA function that occur as a result of repeated exposure to opioids. Moreover, a postdoctoral training plan is proposed that involves a rigorous program of structure activities designed to facilitate the applicant's transitin from postdoctoral trainee to an independent investigator.

描述（由申请人提供）：阿片类药物滥用仍然是一个重大的公共卫生问题。类阿片具有高度滥用和依赖倾向，滥用可导致过量和死亡。成功地治疗药物滥用往往由于难以促进目前的吸毒者持续戒烟而受到阻碍。许多因素导致阿片类药物继续滥用和戒断期后阿片类药物重新使用（复发）。了解这些因素将有助于开发更有效的治疗方法。长期使用阿片类药物与神经内分泌功能的显著变化有关，特别是下丘脑-垂体-肾上腺（HPA）轴的活动，这些变化与戒断和继续使用药物有关。虽然HPA激活和戒断之间的联系已经建立，但还不清楚HPA激活可能发挥的作用。一种可能性是HPA激活作为触发器，消除了戒断的一些表现， 转，促进吸毒/复吸。本申请中的研究将检查阿片类药物依赖和戒断过程中HPA轴活性的变化，并将HPA轴活性的变化与对行为和生理措施的影响进行比较。因此，这项研究将为未来的研究奠定基础，研究HPA轴的激活可能在介导从禁欲到吸毒的过渡中发挥的作用。目的1中的研究将确定吗啡和纳洛酮对HPA轴活性以及行为和生理测量的急性作用。目标2中的研究将检查在每天给予吗啡期间和停止每天吗啡治疗后，行为、生理和内分泌测量发生的变化。将比较不同吗啡治疗期间HPA轴活性的变化与已被确立为阿片类药物依赖和戒断的可靠指标的行为和生理测量。这些研究将提供关于由于重复暴露于阿片类药物而发生的HPA功能变化的基础研究。此外，一个博士后培训计划，提出了一个严格的计划，旨在促进申请人从博士后实习生的过渡到一个独立的调查机构的活动。