Chronic adolescent stress increases exploratory behavior but does not appear to change the acute stress response in adult male C57BL/6 mice

Abstract

Chronic stress exposure in adolescence can lead to a lasting change in stress responsiveness later in life and is associated with increased mental health issues in adulthood. Here we investigate whether the Chronic Social Instability (CSI) paradigm influences the behavioral and molecular responses to novel acute stressors in mice, and whether it alters physiological responses influenced by the noradrenergic system. Using large cohorts of mice, we show that CSI mice display a persistent increase in exploratory behaviors in the open field test alongside small but widespread transcriptional changes in the ventral hippocampus. However, both the transcriptomic and behavioral responses to novel acute stressors are indistinguishable between groups. In addition, the pupillometric response to a tail shock, known to be mediated by the noradrenergic system, remains unaltered in CSI mice. Ultra-high performance liquid chromatography analysis of monoaminergic neurotransmitter levels in the ventral hippocampus also shows no differences between control or CSI mice at baseline or in response to acute stress. We conclude that CSI exposure during adolescence leads to persistent changes in exploratory behavior and gene expression in the hippocampus, but it does not alter the response to acute stress in adulthood and is unlikely to alter the function of the noradrenergic system.

The social instability stress paradigm in rat and mouse: A systematic review of protocols, limitations, and recommendations

“…SIS 49D applied to adolescent male or female C57BL/6J mice also decreased the distance travelled in the center zone of the open field arena in stressed male and female mice compared to non-stressed controls when measured several weeks after the SIS protocol, and this anxiogenic effect was dependent on the estrous cycle in female mice ( Yohn et al, 2019 ). In contrast, SIS 49D , albeit a slightly modified version with random cage distribution, applied to two large cohorts of adolescent male C57BL/6J mice consistently increased time spent in the center zone of the open field arena compared to non-stressed controls, when measured during the active (dark) phase five weeks following SIS ( Sturman et al, 2021 ). During the novelty suppressed feeding test, SIS 49D applied to adolescent male CD1 mice or adolescent male and female C57BL/6J mice consistently increased latency to initiate food consumption ( Schmidt et al, 2007 , 2010a ; Sterlemann et al, 2008 ; Yohn et al, 2019 ).…”

“…However, the two articles that applied a relative short SIS mouse protocol ( Chatterjee et al, 2009 ; de Lima and Massoco, 2017 ) unfortunately assessed a limited number of parameters compared to the relative long protocol studies, and did not assess the impact of SIS on social behavior, gene expression, neurogenesis or adrenal weight. Furthermore, relative long SIS protocols increase anxiety-like behavior ( Schmidt et al, 2007 ; Sterlemann et al, 2008 , 2010 ; Yohn et al, 2019 ) or decrease anxiety-like behavior ( Sturman et al, 2021 ) in SIS mice compared to non-stressed controls, whereas a relative short SIS protocol did not affect this parameter ( de Lima and Massoco, 2017 ).…”

Sperm chromatin accessibility’s involvement in the intergenerational effects of stress hormone receptor activation

“…Mice were placed into the light compartment at the start of the test. Videos were then analyzed using animal pose estimation software DeepLabCut [ 72 ].…”