Social subordination produces distinct stress-related phenotypes in female rhesus monkeys

Abstract

Social subordination in female macaques is imposed by harassment and the threat of aggression and produces reduced control over one's social and physical environment and a dysregulation of the limbic-hypothalamic-pituitary-adrenal axis resembling that observed in people suffering from psychopathologies. These effects support the contention that this particular animal model is an ethologically relevant paradigm in which to investigate the etiology of stress-induced psychological illness related to women. Here, we sought to expand this model by performing a discriminate analysis (DA) on 33 variables within three domains; behavioral, metabolic/anthropomorphic, and neuroendocrine, collected from socially housed female rhesus monkeys in order to assess whether exposure to social subordination produces a distinct phenotype. A receiver operating characteristic (ROC) curve was also calculated to determine each domain's classification accuracy. DA found significant markers within each domain that differentiated dominant and subordinate females. Subordinate females received more aggression, showed more submissive behavior, and received less of affiliation from others than did dominant females. Metabolic differences included increased leptin, and reduced adiponectin in dominant compared to subordinate females. Dominant females exhibited increased sensitivity to hormonal stimulation with higher serum LH in response to estradiol, cortisol in response to ACTH, and increased glucocorticoid negative feedback. Serum oxytocin, CSF DOPAC and serum PACAP were all significantly higher in dominant females. ROC curve analysis accurately predicted social status in all three domains. Results suggest that socially house rhesus monkeys represent a cogent animal model in which to study the physiology and behavioral consequences of chronic psychosocial stress in humans.

Establishment of stable dominance interactions in prairie vole peers: Relationships with alcohol drinking and activation of the paraventricular nucleus of the hypothalamus

“…For example, dominant female rhesus macaques have higher serum levels of OT than subordinates (Michopoulos, Checchi, Sharpe, & Wilson, 2011; Michopoulos, Higgins, Toufexis, & Wilson, 2012), the receipt of aggression in a social defeat procedure induces OT release in the lateral septum of male rats (Ebner, Wotjak, Landgraf, & Engelmann, 2000), and intracerebroventricular administration of OT increases aggressive behavior in dominant (but not subordinate) squirrel monkeys (Winslow & Insel, 1991). These findings suggest that activation of OT cells in the PVN could contribute to the assertion of dominance observed in prairie voles in the present study.…”

Small changes in meal patterns lead to significant changes in total caloric intake. Effects of diet and social status on food intake in female rhesus monkeys

“…Social groups were established approximately 3 years prior to the study using previously described methods (Jarrell et al, 2008). These animals formerly served as subjects in NIH-funded studies to determine the effects of psychosocial stress, induced by social subordination, on a number of behavioral, metabolic, and reproductive outcomes (Collura, Hoffman, & Wilson, 2009; Jarrell et al, 2008; Michopoulos, Berga, Kaplan, & Wilson, 2009; Michopoulos, Checchi, Sharpe, & Wilson, 2011; Michopoulos, Toufexis, & Wilson, 2012b; Michopoulos & Wilson, 2011; Michopoulos et al, in 2012a) that required brief hormone replacement therapy with estradiol and/or progesterone. For the present study, females were untreated and had not received hormone replacement therapy for approximately 8 months.…”

Stress-induced alterations in estradiol sensitivity increase risk for obesity in women

“…Macaque social groups are organized by a linear dominance hierarchy that is imposed by the threat of aggression or harassment from higher-ranking individuals towards lower-ranking individuals within the hierarchy [78, 79]. Subordinate social status in female macaques results in an array of adverse health outcomes that mimic those seen in humans [80] (summarized in Table 1), such as a pro-inflammatory state [81]. Importantly, subordination in female macaques is associated with alteration in LHPA axis activity [82, 83], including hypercortisolemia due to diminished glucocorticoid negative feedback of the LHPA axis [84, 85], altered sensitivity to ACTH [82, 86], and increased adrenal size [87].…”