Effects of ovariectomy, social instability and social status on female Macaca fascicularis social behavior

Shively, Carol A.; Kaplan, Jay R.; Adams, Michael R.

doi:10.1016/0031-9384(86)90492-0

Cited by 41 publications

(25 citation statements)

References 14 publications

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“…After ovariectomy, dominants are still more aggressive than subordinates; however, OVX dominants have higher indices of 5-HT neurotransmission than OVX subordinates, the opposite of what is observed in intact females. 3,33 These results suggest that the relation among 5-HT, ovarian hormones, and behavior is not invariant. Among female monkeys, ovarian steroids may mediate the relation between social status and 5-HT.…”

Section: Discussionmentioning

confidence: 90%

Soy and social stress affect serotonin neurotransmission in primates

Shively

Mirkes

et al. 2003

Pharmacogenomics J

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Stress and sex steroidal milieu can each influence mood in women. The purpose of this study was to compare the effect of long-term conjugated equine estrogen (CEE), soy phytoestrogen (SPE), and social subordination stress on dorsal raphe serotonin neurotransmission of ovariectomized cynomolgus monkeys. Tryptophan hydroxylase (TPH) and serotonin reuptake transporter (SERT) protein content were determined, and the in vitro degradation of macaque SERT protein was examined in the presence and absence of protease inhibitors, serotonin (5-HT), and citalopram. Like CEE, SPE increased TPH protein levels. Social subordinates had markedly lower TPH protein levels than dominants regardless of hormone replacement. Therefore, these two variables had independent and additive effects. CEE and SPE increased SERT, and social status had no effect. Thus, the hormoneinduced increase in SERT was accompanied by increased 5-HT synthesis and neuronal firing, which appears biologically reasonable as 5-HT prevented SERT degradation in vitro.

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Section: Discussionmentioning

confidence: 90%

Soy and social stress affect serotonin neurotransmission in primates

Shively

Mirkes

et al. 2003

Pharmacogenomics J

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“…The intent of this analysis was to determine whether the effect of psychosocial stress (new group formation and attendant changes in social status) on activation of the LHPA axis [39,40] was influenced by SERT genotype. Because corticotropin-releasing hormone (CRH) is known to be anorexic [41,42], we focused on metabolic and body weight-related endpoints.…”

Section: Outcome Measuresmentioning

confidence: 99%

Polymorphisms in the serotonin reuptake transporter gene modify the consequences of social status on metabolic health in female rhesus monkeys

Jarrell¹,

Hoffman²,

Kaplan³

et al. 2008

Physiology & Behavior

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109

163

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Individuals vary substantially in their vulnerability to physical and psychosocial stressors. The causes of such variation in susceptibility to stress are poorly understood, but are thought to relate in part to genetic factors. The present study evaluated the extent to which polymorphisms in the gene encoding the serotonin reuptake transporter (5HTTLPR or SERT) modulated physiologic responses to the imposition of psychosocial stress (social reorganization and subordinate social status) in female rhesus monkeys. Forty females, drawn from the middle ranking genealogies of several large social groups, were reorganized into eight groups containing 5 monkeys each; four groups were comprised entirely of animals homogeneous for the long promoter variant in the SERT gene (l/l), while the other four groups had monkeys with at least one allele of the short promoter variant (l/s or s/s). Females were sequentially introduced into these new groups in random order and dominance ranks were established within several days. During the ensuing 6 weeks, dominant monkeys exhibited elevated rates of aggression while subordinates displayed high rates of submission. Notably, females with the s-variant SERT genotype, collapsed across social status positions, exhibited the highest overall rates of both aggression and submission. Although neither social status nor SERT genotype influenced morning cortisol concentrations, glucocorticoid negative feedback was reduced significantly in subordinate compared to dominant females irrespective of genotype. All animals lost weight and abdominal fat across the experiment. However, decreases were greatest in subordinates, regardless of genotype, and least in dominant females with the l/l genotype. Serum concentrations of insulin, glucose, and ghrelin decreased significantly during the group formation process, effects that were independent of genotype or social status. In contrast, social status and genotype interacted to influence changes in serum concentrations of leptin and triiodothyronine (T3), as dominant, l/l females had the highest levels while subordinate s-variant females had the lowest levels. The order in which a female was introduced to her group generally predicted her eventual social rank. However, rank was additionally predicted by pre-experimental T3 and abdominal fat values, but only in the l/l animals. While these findings must be replicated with a larger sample size, the data suggest that the s-variant SERT genotype confers increased vulnerability to the adverse effects of psychosocial stress associated with subordinate status while the l/l genotype benefits the most from the absence of stress conferred by dominant social status. These findings suggest that genetic factors modify the responses of monkeys to social subordination and perhaps other psychosocial stressors.

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“…Social status was determined monthly based on the direction of the outcome of agonistic interactions, as previously reported (Shively et al 1986). Social status was averaged during the pre-treatment and treatment phases for analysis (Shively et al 2014).…”

Section: Behavioral Observationsmentioning

confidence: 99%

“…We investigated adult female cynomolgus monkeys (Macaca fascicularis), an established model of spontaneous depression, social stress, and age-related physical dysfunction (Shively et al 1986(Shively et al , 2008Willard and Shively 2012). The relationships between depressive behavior and the effects of the commonly prescribed SSRI, sertraline HCl, on physical function were assessed over a 3-year study with an 18-month treatment phase using a longitudinal, stratified, placebo-controlled design.…”

Section: Introductionmentioning

confidence: 99%

Relationships of depressive behavior and sertraline treatment with walking speed and activity in older female nonhuman primates

et al. 2017

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Depression is the most common mental health problem in aging persons and is a leading risk factor for physical disability, especially in women. Though antidepressant drugs such as serotonin reuptake inhibitors (SSRI) are commonly prescribed, epidemiological evidence reveals mixed effects of long-term antidepressant use on physical function and activity, possibly depending on depressive status. The purpose of this preclinical trial was to determine the relationships of depressive behavior and the potential for an SSRI treatment to modulate walking speed and activity patterns in older adult female cynomolgus monkeys (Macaca fascicularis). We evaluated the effects of depression and a commonly prescribed SSRI, sertraline HCl (20 mg/kg/day p.o.), on (a) walking speed, (b) accelerometry-derived activity (counts) and sedentariness (daytime 60-s sedentary epochs), and (c) observed locomotor and sedentary behaviors (% time) in adult female depressed and nondepressed monkeys (n = 42; 17.2 ± 1.8 years) during an 18 month pretreatment phase and an 18 month treatment phase using a longitudinal, stratified placebo-control study design. Monkeys that were depressed prior to treatment (19/42) subsequently had slower walking speeds (F D [1, 38] = 4.14; p ≤ 0.05) and tended to be more sedentary during the daytime (F D [1, 38] = 3.63; p ≤ 0.06). Sertraline did not affect depressive behaviors, walking speed, accelerometry-derived physical activity or sedentariness, or time observed in total locomotor or sedentary behavior (all p > 0.10). This study provides the first experimental demonstration of relationships between nonhuman primate behavioral depression and walking speed, activity, and sedentariness and provides evidence for a lack of an effect of SSRI treatment on these phenotypes.

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Effects of ovariectomy, social instability and social status on female Macaca fascicularis social behavior

Cited by 41 publications

References 14 publications

Soy and social stress affect serotonin neurotransmission in primates

Soy and social stress affect serotonin neurotransmission in primates

Polymorphisms in the serotonin reuptake transporter gene modify the consequences of social status on metabolic health in female rhesus monkeys

Relationships of depressive behavior and sertraline treatment with walking speed and activity in older female nonhuman primates

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