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.

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 在人类中出现了两个相互排斥的假说，暗示内源性阿片(EO)系统在SIB中的作用。疼痛假说认为，Eos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，自我管理假说提出，个体参与SIB可以提升Eos，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猴子优先将咬合定向到穴位(Marinus等人)。2000)，这被认为涉及在人类体内释放Eos(Ulett等人)。1998年)。我们还报告了血浆β-内啡肽水平的降低(Tiefenbacher等人。2003a)和脑脊液甲硫氨酸脑啡肽(Tiefenbacher et al.2003年b)在患有SIB的猴子中。这些发现表明，猴子的SIB可能可以用自我给药假说得到最好的解释，自我给药假说有助于增加β-内啡肽水平。基于脑啡肽和强啡肽基因敲除小鼠的发现，大脑阿片受体上调(Brady等人。1999年；Clarke等人。2003)，我们假设Mu-阿片受体(MOR)在患有SIB的猴子的大脑中上调，从而增加了咬伤后释放β-内啡肽的积极作用。