TY - JOUR
T1 - The visible burrow system
T2 - A view from across the hall
AU - Herman, James P.
AU - Tamashiro, Kellie L.
N1 - Funding Information:
The authors would like to thank Randall and all his trainees (especially Mary Nguyen, Eric Krause, Susan Melhorn, Karen Scott, Jessica Hegeman, Ryan Makinson) for their insight and camaraderie throughout the years. We would like to acknowledge support from MH101729 (JPH) and MH049698 (JPH), which funded the CVS experiments, as well as Randall's long-standing funding by NIDDK.
Publisher Copyright:
© 2017
PY - 2017/9/1
Y1 - 2017/9/1
N2 - 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.
AB - 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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U2 - 10.1016/j.physbeh.2017.01.021
DO - 10.1016/j.physbeh.2017.01.021
M3 - Review article
C2 - 28089702
AN - SCOPUS:85012878887
SN - 0031-9384
VL - 178
SP - 103
EP - 109
JO - Physiology and Behavior
JF - Physiology and Behavior
ER -