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.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 人类中出现了两种相互排斥的假设，暗示内源性阿片类药物 (EO) 系统在 (SIB) 中的作用。疼痛假说认为，EO 升高会导致痛觉减退，导致 SIB 作为一种自我刺激形式。相比之下，自我管理假说认为，个体参与 SIB 是为了提高 EO 并缓解负面情绪。重要的是，我们已经证明患有 SIB 的猴子的 EO 系统可能会发生改变。 SIB 猴优先咬住穴位（Marinus 等，2000），这被认为涉及人类体内 EO 的释放（Ulett 等，1998）。 我们还报道了患有 SIB 的猴子中血浆 β-内啡肽 (Tiefenbacher et al. 2003a) 和脑脊液甲硫氨酸脑啡肽 (Tiefenbacher et al. 2003b) 水平降低。这些发现表明，猴子的 SIB 可以通过自我给药假说来最好地解释，该假说有助于增加 β-内啡肽水平。基于脑啡肽和强啡肽基因敲除小鼠大脑阿片受体上调的发现（Brady 等人，1999；Clarke 等人，2003），我们假设 mu-阿片受体（MOR）在小鼠大脑中上调。患有 SIB 的猴子，增加咬伤后 β-内啡肽释放的积极作用。