THE EFFECTS OF FENTANYL, AN OPIOID AGONIST, ON SIB

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 两个相互排斥的假说已经出现在人类暗示的作用，内源性阿片（EO）系统（SIB）。疼痛假说提出，升高的EO导致痛觉减退，导致SIB作为一种自我刺激形式。与此相反，自我管理假说提出，个人从事SIB，以提高EO和缓解负面情绪。重要的是，我们已经表明，EO系统可能会改变与SIB的猴子。SIB猴优先将咬合指向穴位（Marinus等人，2000年），这被认为涉及人体内EO的释放（Ulett等人，1998年）。 我们还报告了SIB猴的血浆β-内啡肽（Tiefenbacher et al. 2003 a）和CSF甲硫氨酸脑啡肽（Tiefenbacher et al. 2003 b）水平降低。这些发现表明，我们的猴子中的SIB可能是最好的解释自我管理的假设，这有助于增加β-内啡肽水平。基于脑啡肽和强啡肽基因敲除小鼠的发现，即脑阿片受体上调（布雷迪等人，1999; Clarke等人，2003），我们假设μ阿片受体（莫尔）在患有SIB的猴子的脑中上调，增加了咬后β-内啡肽释放的积极作用。

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.