NOREPINEPHRINE IN STRESS-INDUCED AMENORRHEA OF MACAQUES

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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.