Role for the HPA Axis in Methamphetamine Reinforcement

美国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，希望将这一进展的成果应用于甲基苯丙胺滥用的预防和治疗。这一“甲基苯丙胺倡议”旨在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该药物使用、后果、预防和治疗的最新信息。这项倡议的提出是对滥用甲基苯丙胺已成为一个极其严重和日益严重的问题的关切作出的反应。虽然甲基苯丙胺最初主要在美国西南部的选定城市地区使用，但现在在中西部的许多地区，在城市和农村环境中，以及在非常不同的人群中，都观察到高度滥用甲基苯丙胺。这是针对“甲基苯丙胺倡议”而开发的修订申请，描述了旨在确定应激和随后在甲基苯丙胺强化行为神经生物学中下丘脑-垂体-肾上腺（EPA）轴激活的潜在作用的实验。这一应用的主要假设是EPA轴以类似于tee的方式影响甲基苯丙胺的强化功效。应激对冰毒强化的影响将在冰毒自我释放的三个方面进行研究，即冰毒观察行为的获得、维持和恢复。在本申请中，我们重点介绍了我们在过去10年左右进行的研究，这些研究证明了压力、CRF和皮质酮在可卡因自我给药中的重要作用，这些研究使用了我们开发和/或改进的方法来调查这些因素。本应用程序描述了使用非常相似的程序来研究这些因素对甲基苯丙胺强化的影响的实验。总之，这些实验将增加对应激和随后的EPA轴激活如何影响甲基苯丙胺强化的认识，并可能为治疗人类甲基苯丙胺滥用和戒断提出新的药物疗法。

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.