THE EFFECTS OF FENTANYL, AN OPIOID AGONIST, ON SIB

芬太尼（一种阿片类药物激动剂）对 SIB 的影响

• 批准号: 8358019
• 负责人: Melinda Ann Novak
• 金额: $ 5.4万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8358019
• 关键词: Acupressure; Agonist; Bite; Brain; Dynorphins; Emotions; Enkephalins; Fentanyl; Funding; Grant; Human; Individual; Knockout Mice; Methionine Enkephalin; Monkeys; National Center for Research Resources; New England; Opioid; Opioid Receptor; Pain; Plasma; Primates; Principal Investigator; Reporting; Research; Research Infrastructure; Resources; Role; Self Administration; Self Stimulation; Source; System; United States National Institutes of Health; base; beta-Endorphin; cost; endogenous opioids; mu opioid receptors

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Two mutually exclusive hypotheses have emerged in humans implicating a role of the endogenous opioid (EO) system in (SIB). The pain hypothesis proposes that elevated EOs result in hypoalgesia leading to SIB as a form of self stimulation. In contrast, the self-administration hypothesis proposes that individuals engage in SIB to elevate EOs and relieve negative emotions. Importantly, we have shown that the EO system may be altered in monkeys with SIB. SIB monkeys preferentially directed biting to acupressure points (Marinus et al. 2000), which is thought to involve release of EOs in humans (Ulett et al. 1998). We have also reported reduced levels of plasma beta-endorphin (Tiefenbacher et al. 2003a) and CSF met-enkephalin (Tiefenbacher et al. 2003b) in monkeys with SIB. These findings suggest that SIB in our monkeys may be best explained by the self-administration hypothesis which serves to increase beta-endorphin levels. Based on findings in enkephalin and dynorphin knockout mice, that brain opioid receptors are up-regulated (Brady et al. 1999; Clarke et al. 2003), we hypothesized that mu-opioid receptors (MOR) are up-regulated in the brains of monkeys with SIB, increasing the positive effects of beta-endorphin release after biting.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 人类中出现了两个相互排斥的假设，这暗示了（SIB）中内源性阿片类药物（EO）的作用。疼痛假设提出，EOS升高会导致低差导致SIB作为一种自我刺激的一种形式。相比之下，自我管理假设提出，个人参与SIB来提升EOS并减轻负面情绪。重要的是，我们已经表明，在使用SIB的猴子中，EO系统可能会改变。 Sib猴子优先针对咬合点（Marinus等，2000），这被认为涉及人类中EOS的释放（Ulett等，1998）。 我们还报道了在具有SIB的猴子中，血浆β-内啡肽（Tiefenbacher等人2003a）和CSF Met-Enkephalin（Tiefenbacher等，2003b）的水平降低。这些发现表明，我们的猴子中的同胞可以通过自我管理假设来最好地解释，该假设有助于提高β-内啡肽水平。基于Enkephalin和Dynorphin敲除小鼠的发现，大脑阿片类受体被上调（Brady等，1999; Clarke etal。2003），我们假设Mu-Apioid受体（MOR）在猴子的脑中被sib的脑中脑升高，从而增加了Beta-endorphiterphit的阳性效应。