Preclinical laboratory assessments of predictors of social rank in female cynomolgus monkeys

Abstract

Physiological and behavioral differences between dominant and subordinate monkeys have been useful in preclinical models investigating numerous disease states. In captivity, it has been inferred that subordinate monkeys live in a context of chronic social stress and may be at risk for a variety of dysfunctions; however, the factors that influence eventual rank are not entirely known. The goal of the present study was to first evaluate several phenotypic characteristics as potential trait markers for eventual social rank and then to determine the consequences of social hierarchy on these measures (i.e., state markers). Baseline estradiol, progesterone, cortisol and testosterone concentrations were obtained from 16 pair-housed female cynomolgus monkeys before and after introduction into new social groups (n = 4/group). Furthermore, effects of the initial week of social rank establishment on outcome measures of cognitive performance and homecage activity were examined. Baseline body weight and mean serum estradiol concentrations were the only statistically significant predictors of eventual rank, with future subordinate monkeys weighing less and having higher estradiol concentrations. During initial hierarchy establishment, future subordinate monkeys had increased morning and afternoon cortisol concentrations, increased locomotor activity and impaired cognitive performance on a working memory task. After 3 months of social housing, subordinate monkeys had blunted circulating estradiol and progesterone concentrations. These findings demonstrate differential effects on gonadal hormones and cortisol as a function of social context in normally cycling female monkeys. Furthermore, disruptions in cognitive performance were associated with subordinate status, suggesting strong face validity of this model to the study of factors related to the etiology and treatment of human diseases associated with chronic stress. Am. J. Primatol. 78:402-417, 2016. © 2015 Wiley Periodicals, Inc.

Contrasting effects of Western vs Mediterranean diets on monocyte inflammatory gene expression and social behavior in a primate model

“…To overcome the limitations of human studies, we designed a randomized preclinical trial in cynomolgus macaques ( Macaca fascicularis ), a well-established model of dietary and behavioral influences on health in which we can carefully control diet and the environment. Macaques are excellent models for human health and disease as they share many core genetic, physiological, and behavioral phenotypes with humans ( Jarczok et al, 2018 ; Kromrey et al, 2016 ; Shively, 1998 ; Shively and Day, 2015 ; Willard and Shively, 2012 ). In this study, we conducted a whole-diet manipulation to directly and simultaneously compare the behavioral and physiological effects of Mediterranean and Western diets, formulated to mimic human diet patterns.…”

Effects of the α-2 Adrenergic Receptor Agonists Lofexidine and Guanfacine on Food-Cocaine Choice in Socially Housed Cynomolgus Monkeys

“…Although subordinate monkeys undoubtedly experience chronic social stress, social rank-related differences in the effects of stress may be more prominently mediated by changes in hypothalamic-pituitary-adrenal axis function. For example, higher cortisol concentrations are observed in both male and female subordinates during initial social housing (Czoty et al, 2009;Kromrey et al, 2016). Moreover, male subordinate monkeys showed greater adrenal gland responsiveness to adrenocorticotropic hormone after suppression with the glucocorticoid agonist dexamethasone (Czoty et al, 2009).…”

Mediterranean Diet, Stress Resilience, and Aging in Nonhuman Primates

“…The monkeys were randomly assigned to the WEST or the MED diet group for 31 months (the equivalent of about 9 human years; Supplementary Table 1). The two groups were confirmed to be balanced on pretreatment characteristics that reflected overall health including body weight, body mass index, age, basal cortisol concentration, and plasma lipid concentrations measured as previously described (40,41). All animal manipulations were Supplementary Table 2).…”