A closer look at the subordinate population within the visible burrow system

Melhorn, Susan J.; Elfers, Clinton; Scott, Karen A.; Sakai, Randall R.

doi:10.1016/j.physbeh.2017.01.039

Cited by 13 publications

(20 citation statements)

References 36 publications

(43 reference statements)

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“…However, these effects may depend on the type of stressor one is exposed to. Recently, Melhorn et al (2017) demonstrated that OMEGA males, SUBs that experienced the most wounding and most severe body weight loss had significantly higher elevations of NPY mRNA within the amygdala that traditional SUBs. Whether this reflects a beneficial, but insufficient compensatory mechanism or a maladaptive one is unclear.…”

Section: Discussionmentioning

confidence: 99%

“…Previous VBS studies have demonstrated that SUB males have enhanced HPA axis activity and that this corresponds with elevated CRH mRNA expression within the paraventricular nucleus of the hypothalamus (PVN) and the central nucleus of the amygdala (CeA). Occasionally, one subordinate male will be the main recipient of attacks in the burrow, and is referred to as the OMEGA; OMEGA males incur more wounds, more severe weight loss and exhibit depressive-like behaviours at the end of the 2 wk VBS housing period (Melhorn et al 2017). …”

Section: Introductionmentioning

confidence: 99%

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Susceptibility or resilience? Prenatal stress predisposes male rats to social subordination, but facilitates adaptation to subordinate status

Scott

Kloet

Smeltzer

et al. 2017

Physiology & Behavior

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Mood disorders such as major depressive disorder (MDD) affect a significant proportion of the population. Although progress has been made in the development of therapeutics, a large number of individuals do not attain full remission of symptoms and adverse side effects affect treatment compliance for some. In order to develop new therapies, there is a push for new models that better reflect the multiple risk factors that likely contribute to the development of depressive illness. We hypothesized that early life stress would exacerbate the depressive-like phenotype that we have previously observed in socially subordinate (SUB), adult male rats in the visible burrow system (VBS), a semi-natural, ethologically relevant environment in which males in a colony form a dominance hierarchy. Dams were exposed to chronic variable stress (CVS) during the last week of gestation, resulting in a robust and non-habituating glucocorticoid response that did not alter maternal food intake, body weight or litter size and weight. As adults, one prenatal CVS (PCVS) and one non-stressed (NS) male were housed in the VBS with adult females. Although there were no overt differences between PCVS and NS male offspring prior to VBS housing, a greater percentage of PCVS males became SUB. However, the depressive-like phenotype of SUB males was not exacerbated in PCVS males; rather, they appeared to better cope with SUB status than NS SUB males. They had lower basal plasma corticosterone than NS SUB males at the end of VBS housing. In situ hybridization for CRH in the PVN and CeA did not reveal any prenatal treatment or status effects, while NPY expression was higher within the MeA of dominant and subordinate males exposed to the VBS in comparison with controls, but with no effect of prenatal treatment. These data suggest that prenatal chronic variable stress may confer resilience to offspring when exposed to social stress in adulthood.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Susceptibility or resilience? Prenatal stress predisposes male rats to social subordination, but facilitates adaptation to subordinate status

Scott

Kloet

Smeltzer

et al. 2017

Physiology & Behavior

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“…Recent work from Melhorn (this issue) has further clarified the issue of heterogenity within subordinate subpopulations [16]. On the basis of wound burden and location, her study identifies a more severe subordinate stress group (referred to as Omegas) that have markedly potentiated weight loss relative to DOM and other subordinates (SRS), including rather marked loss of lean body mass.…”

Section: The Vbs Stress ‘Phenotype’mentioning

confidence: 99%

“…Importantly, identified Omegass are also stress hyporesponsive, having a negligible corticosterone response to restraint challenge. These data suggest the hierarchical structure extends beyond a single dominant and submissive phenotype, and that the Omega individuals may be the most severely affected of all groups [16]. …”

Section: The Vbs Stress ‘Phenotype’mentioning

confidence: 99%

“…This is of course a maladaptive and potentially life-threatening condition. In addition, the loss of lean body mass seen in the Omega subordinates [16] represents a severe metabolic challenge, undeniably maladaptive. The nature and severity of the Omega phenotype recalls the failure phase of Selye’s General Adaptation Syndrome, wherein the system is pushed beyond the ability to adapt effectively [18].…”

Section: The Vbs Stress ‘Phenotype’mentioning

confidence: 99%

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The visible burrow system: A view from across the hall

Herman

Tamashiro

2017

Physiology & Behavior

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The visible burrow system (VBS) is an ethologically relevant social stress model that creates a distinct dominance hierarchy in rats. Randall Sakai’s laboratory performed an impressive series of studies documenting the very different impact of VBS exposure on the brain and behavior of dominants (DOM) and subordinates (SUBs). Hierarchy formation causes pronounced changes in metabolism in SUBs relative to both DOMs and unstressed controls, resulting in marked weight loss and metabolic imbalance. Stress testing revealed multiple phenotypes in the VBS, including DOMs, stress-responsive SUBs and stress-non-responsive SUBs. Stress-responsive SUBs have adrenal hypertrophy and elevated baseline corticosterone, consistent with prolonged HPA axis activation; however, peak acute stress responses are not sensitized. In contrast, stress non-responsive individuals do not mount a response to an acute stress, suggesting HPA axis hypofunction. In brain, SUBs exhibit a pattern of gene regulation consistent with impaired stress inhibition (e.g., hippocampal adrenocorticosteroid receptor down-regulation and dendritic retraction) and drive of stress pathways (e.g., increased locus coeruleus tyrosine hydroxylase expression). The non-responsive phenotype is distinguished by down-regulation of paraventricular nucleus corticotropin releasing hormone expression and enhanced neuropeptide Y expression in amygdala. The brain ‘signature’ created by VBS hierarchy formation differed substantially from that of another well-studied chronic stress model (chronic variable stress). Thus, the impact of VBS is mediated by neurocircuit mechanisms at least in part distinct that of other chronic stress modalities, and suggests that the nature of the stressor may be an essential consideration in development of treatment strategies for stress-related diseases.

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