Role for the HPA Axis in Methamphetamine Reinforcement

HPA 轴在甲基苯丙胺强化中的作用

• 批准号: 6515790
• 负责人: Nicholas E. Goeders
• 金额: $ 32.06万
• 依托单位: LOUISIANA STATE UNIV HSC SHREVEPORT
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-01 至 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6515790
• 关键词: adrenalectomy; adrenocorticotropic hormone; autoradiography; behavioral /social science research tag; biological models; corticosteroid receptors; corticosterone; drug abuse; electrostimulus; hormone regulation /control mechanism; hypothalamic pituitary adrenal axis; laboratory rat; methamphetamine; microdialysis; molecular psychobiology; neurobiology; neurochemistry; neuroendocrine system; neuropsychological tests; neurotransmitter receptor; psychological reinforcement; receptor expression; relapse /recurrence; self medication; stress; substance abuse related behavior

The National Institute on Drug Abuse (NMA) recently launched an Institute-wide initiative to expand scientific reseal on the behavioral neurobiology of methamphetamine with the hopes of applying the results of this march to the prevention and treatment of methamphetamine abuse. This "Methamphetamine Initiative" is aimed at increasing scientific knowledge regarding methamphetamine and providing the public and health care practitioners with the latest available information about the drug's use, consequences, prevention, and treatment. This initiative was issued in response to the concern that the abuse of methamphetamine has become an extremely serious and growing problem. Although the drug was first used primarily in selected urban areas in the Southwestern part of the United States, high levels of methamphetamine abuse are now being observed in many areas of the Midwest, in both urban and rural settings, and by very diverse segments of the population. This is a revised application developed in response to this "Methamphetamine Initiative" and describes experiments designed to determine the potential role for stress and the subsequent activation of the hypothalamo-pituitary-adrenal (EPA) axis in the behavioral neurobiology of methamphetamine reinforcement. The primary hypothesis for this application is that the EPA axis influences the reinforcing efficacy of methamphetamine in a manner similar to tee. The influence of stress in methamphetamine reinforcement will be investigated during all three aspects of methamphetamine self-eon: namely the acquisition, maintenance and reinstatement of methamphetamine-seeing behavior. In this application, we highlight research we have conducted during the last 10 years or so demonstrating an important role for stress, CRF and corticosterone in cocaine self-administration using methodology we have developed and/or refined to investigate these Factors. This application describes experiments designed to investigate the influence of these factors in methamphetamine reinforcement using very similar procedures. Together, these experiments will increase knowledge of how stress and the subsequent activation of the EPA axis influence methamphetamine reinforcement and may also suggest novel pharmacotherapies for the treatment of methamphetamine abuse and withdrawal in humans.

国家药物滥用研究所（NMA）最近发起了一项全研究所范围的倡议，以扩大对甲基苯丙胺行为神经生物学的科学研究，希望将这次游行的结果应用于预防和治疗甲基苯丙胺滥用。这一“甲基苯丙胺倡议”的目的是增加有关甲基苯丙胺的科学知识，并向公众和保健从业人员提供有关毒品使用、后果、预防和治疗的最新信息。这一倡议是针对甲基安非他明滥用已成为一个极其严重和日益严重的问题这一关切而提出的。虽然这种药物最初主要是在美国西南部的某些城市地区使用的，但在中西部的许多地区，无论是在城市还是在农村，都观察到大量的甲基安非他明滥用，而且是由各种不同的人口群体使用的。这是一个修订后的应用程序开发响应这个“甲基苯丙胺倡议”，并描述了实验设计，以确定潜在的作用，压力和随后的激活下丘脑-垂体-肾上腺（EPA）轴的行为神经生物学的甲基苯丙胺加固。本申请的主要假设是EPA轴以类似于tee的方式影响甲基苯丙胺的增强功效。压力在甲基苯丙胺强化中的影响将在甲基苯丙胺自我过程的所有三个方面进行研究：即甲基苯丙胺看到行为的获得，维持和恢复。在本申请中，我们强调了我们在过去10年左右进行的研究，证明了压力，CRF和皮质酮在可卡因自我管理中的重要作用，使用我们开发和/或改进的方法来调查这些因素。本申请描述了使用非常相似的程序设计来调查这些因素在甲基苯丙胺强化中的影响的实验。总之，这些实验将增加如何压力和随后的EPA轴激活影响甲基苯丙胺加固的知识，也可能表明新的药物治疗甲基苯丙胺滥用和人类戒断。