NOREPINEPHRINE IN STRESS-INDUCED AMENORRHEA OF MACAQUES

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。 这是一个新的项目，以确定脑干去甲肾上腺素（NE）系统是否在共同的生活压力（即，节食、适度运动和心理压力）损害生殖轴的活动。我们有大量的证据表明，压力敏感（SS）的女性在中枢神经系统中具有较低的多巴胺能功能。此外，5-羟色胺抑制脑干中蓝斑核（LC）的NE神经元。这意味着SS动物中血清素的减少可能导致LC中NE神经元的慢性过度激活，并且这些神经元的过度激活与焦虑症有关。因此，我们将测试的假设，NE系统在LC的活性升高是负责对应激敏感的猴子的生殖轴的抑制。目标1将进行初步研究，以确定SS和应激恢复（SR）猴NE系统的生理功能，并确定抗焦虑药物reboxalone是否能预防应激诱导的生殖功能障碍（分包给匹兹堡大学的Judy卡梅隆博士）。目的2将确定关键基因和蛋白质的表达在NE神经元的LC和检查纤维密度的应力相关传入神经支配的LC在SS，加上中度和高度SR猴子在存在和不存在的压力。正在分析在存在和不存在压力的情况下实施安乐死的压力抗性和压力敏感动物的蓝斑。

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. This is a new project to determine whether the brain stem norepinephrine (NE) system plays a role in the mechanisms by which common life stresses (i.e., dieting, moderate exercise and psychological stress) impair activity of the reproductive axis. We have substantial evidence that stress sensitive (SS) females have lower serotonergic function in the central nervous system. Moreover, serotonin inhibits the NE neurons of the locus ceruleus (LC) nucleus in the brain stem. This means that the reduction in serotonin in the SS animals may lead to chronic over-activation of NE neurons in the LC, and over-activation of these neurons has been implicated in anxiety disorders. Therefore, we will test the hypothesis that elevated activity of the NE system in the LC is responsible for the suppression of the reproductive axis in stress-sensitive monkeys. Aim 1 will conduct pilot studies to determine the physiological function of the NE system in SS and stress resilient (SR) monkeys and to determine if the antianxiety medication, reboxetine, will prevent stress-induced reproductive dysfunction (subcontracted to Dr. Judy Cameron, Univ Pittsburgh). Aim 2 will determine the expression of pivotal genes and proteins in the NE neurons of the LC and examine the fiber density of stress-related afferent innervation of the LC in SS, plus moderately and highly SR monkeys in the presence and absence of stress. Analysis of the locus ceruleus of stress-resistant and stress sensitive animals euthanized in the presence and absence of stress is underway.