Subordination stress: Behavioral, brain, and neuroendocrine correlates

Blanchard, D. Caroline; Sakai, Randall R.; McEwen, Bruce S.; Weiss, Scott Μ.; Blanchard, Robert J.

doi:10.1016/0166-4328(93)90096-9

Cited by 447 publications

(271 citation statements)

References 22 publications

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“…Studies using the visible burrow system in rats clearly show the adverse metabolic effects of subordination [29][30][31] and complimentary studies using repeated restraint stress provides similar data [41]. All females in the present study lost body weight over the course of 7 weeks but the decrease was greater in subordinate females, regardless of SERT genotype.…”

Section: Discussionsupporting

confidence: 69%

“…In socially housed rhesus monkeys, frequent harassment from dominant individuals results in a lack of environmental control that delays or prevents access to food, shelter, and preferred social partners while increasing the risk of wounding at the hands (and teeth) of higher ranking monkeys trying to preserve their dominant status [27,28]. Within a status hierarchy of monkeys the clearest physiological sign of increased stress on the part of subordinates is a sustained elevation in glucocorticoid release [29][30][31], which is accompanied in females by reproductive suppression, bone loss, psychopathology, and increased risk of cardiovascular disease [14,15,16].…”

Section: Introductionmentioning

confidence: 99%

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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

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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Section: Discussionsupporting

confidence: 69%

Section: Introductionmentioning

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

109

163

View full text Add to dashboard Cite

show abstract

“…Spleens of least attacked subordinates were slightly heavier than those of dominant animals, although not significant, and spleen weight of attacked subordinates was positively correlated with aggression. Blanchard et al [36,37] reported that continuous social stress increased spleen weight. The fact that testes of dominant mice were negatively correlated with aggression may be somewhat surprising.…”

Section: Social Status Effectsmentioning

confidence: 99%

“…Furthermore, we found a negative correlation between testosterone values of both attacked and nonattacked subordinate mice and aggression. Indeed, testosterone levels in rats have been shown to be suppressed by defeat and subordination [36,37]. Parmigiani et al [38] showed that suppression of testosterone also occurs in subordinate mice that are not subjected to attacks.…”

Section: Social Status Effectsmentioning

confidence: 99%

Modulation of aggression in male mice: influence of group size and cage size

Loo

Mol

Koolhaas

et al. 2001

Physiology & Behavior

225

210

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“…These results suggest that the 5-HT innervation may not have as critical a role in postnatal development of female cortex. Moreover, in males, testosterone modulates serotonin levels and with that levels of aggression (Blanchard et al, 1993;Birger et al, 2003). Thus, other cognitive-emotional behavioral features might be under the control of sex hormones as well.…”

Section: Sex Differencesmentioning

confidence: 99%

Neonatal serotonin depletion alters behavioral responses to spatial change and novelty

et al. 2007

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Multiple brain disorders that show serotonergic imbalances have a developmental onset. Experimental models indicate a role for serotonin as a morphogen in brain development. To selectively study the effects of serotonin depletions on cortical structural development and subsequent behavior, we developed a mouse model in which a serotonin neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT), is injected into the medial forebrain bundle (mfb) on the day of birth. Littermates with saline injections into the mfb and age matched mice served as controls. This study characterized the extent and duration of serotonergic denervation after the selective neonatal lesion and investigated effects on exploratory behavior, spatial learning and anxiety in mice of both sexes. We report significant decreases in the serotonergic (5-HT) innervation to cortex and hippocampus, but not to subcortical forebrain structures in 5,7-DHT-lesioned mice. The depletion of 5-HT fibers in cortical areas was long lasting in lesioned mice but autoradiographic binding to high affinity 5-HT transporters was only transiently reduced. Male but not female lesioned mice reduced their exploration significantly in response to spatial rearrangement and object novelty, suggesting increased anxiety in response to change but normal spatial cognition. Our data show that developmental disruptions in the serotonergic innervation of cortex and hippocampus are sufficient to induce permanent, sex specific, behavioral alterations. These results may have significant implications for understanding brain disorders presenting with cortical morphogenetic abnormalities and altered serotonin neurotransmission, such as autism, schizophrenia and affective disorders.

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Subordination stress: Behavioral, brain, and neuroendocrine correlates

Cited by 447 publications

References 22 publications

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

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

Modulation of aggression in male mice: influence of group size and cage size

Neonatal serotonin depletion alters behavioral responses to spatial change and novelty

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