Neuroendocrine responses to fenfluramine challenge are influenced by exposure to chronic social stress in adult male cynomolgus macaques

Abstract

This study was designed to investigate the effect of chronic social stress on central serotonergic responsivity in adult male cynomolgus monkeys ( Macaca fascicularis). The influences of social stress and dominance status (social rank) on adrenocorticotropin hormone (ACTH) and cortisol responses to acute administration of an indirect serotonergic agonist (fenfluramine) were evaluated in 75 cynomolgus macaques that were housed in five-member social groups for 28 mo. These groups either remained stable in composition (No-Stress) or had their composition periodically reorganized in the first (Early-Stress) or second (Late-Stress) halves of the study. At the end of the 23rd month, a fenfluramine challenge was done. Animals in the Late-Stress condition had significantly higher ACTH responses compared to those in the No-Stress condition ( p < .05) and significantly higher cortisol responses compared to those in the Early-Stress condition ( p < .05). No differences between dominant and subordinate animals in ACTH or cortisol responses to challenge were identified. These data suggest that social stress produces a “state”-related augmentation of hypothalamic-pituitary-adrenal responsivity to fenfluramine (serotonergic) challenge in cynomolgus macaques.