Stress inoculation modeled in mice

Abstract

Stress inoculation entails intermittent exposure to mildly stressful situations that present opportunities to learn, practice and improve coping in the context of exposure psychotherapies and resiliency training. Here we investigate behavioral and hormonal aspects of stress inoculation modeled in mice. Mice randomized to stress inoculation or a control treatment condition were assessed for corticosterone stress hormone responses and behavior during open-field, object-exploration and tail-suspension tests. Stress inoculation training sessions that acutely increased plasma levels of corticosterone diminished subsequent immobility as a measure of behavioral despair on tail-suspension tests. Stress inoculation also decreased subsequent freezing in the open field despite comparable levels of thigmotaxis in mice from both treatment conditions. Stress inoculation subsequently decreased novel-object exploration latencies and reduced corticosterone responses to repeated restraint. These results demonstrate that stress inoculation acutely stimulates glucocorticoid signaling and then enhances subsequent indications of active coping behavior in mice. Unlike mouse models that screen for the absence of vulnerability to stress or presence of traits that occur in resilient individuals, stress inoculation training reflects an experience-dependent learning-like process that resembles interventions designed to build resilience in humans. Mouse models of stress inoculation may provide novel insights for new preventive strategies or therapeutic treatments of human psychiatric disorders that are triggered and exacerbated by stressful life events.

Learning to cope with stress modulates anterior cingulate cortex stargazin expression in monkeys and mice

“…Similar learning to cope effects were then found for mice monitored on tail-suspension, open-field, and novel object-exploration tests (Brockhurst et al, 2015). Experimental learning to cope training sessions increase adult monkey hippocampal neurogenesis and alter the expression of genes involved in cell proliferation and survival (Lyons et al, 2010).…”

“…The mesh-screen barrier prevented fighting and wounding during all 11 encounters with the resident stranger but allowed non-contact interactions. Repeated encounters with a same-sex stranger acutely increase plasma levels of the stress hormone corticosterone in male mice (Brockhurst et al, 2015). Immediately after each encounter, subjects were returned to the home cage.…”

“…Subsequent behavioral measures of emotionality on tail-suspension, open-field, and object-exploration tests were collected 2-13 days after completion of the treatment conditions from 12 mice in each condition (Brockhurst et al, 2015). Brains were then collected 3 days after the behavioral tests of emotionality.…”

“…In addition to the qualities or intensities of stress exposure, temporal aspects further contribute to the production of stress vulnerability versus resilience (Burchfield, 1979). Chronic or prolonged stress leads to vulnerability (Brosschot, 2010) whereas intermittent stress exposures interspersed with undisturbed periods of recovery provide repeated opportunities to learn, practice, and improve coping with subsequent gains in emotion regulation and resilience (Lyons et al, 2009; Lyons et al, 2010; Lee et al, 2014; Brockhurst et al, 2015). …”

“…Experimental learning to cope training sessions acutely increase glucocorticoids (Brockhurst et al, 2015) and therefore a secondary exploratory aim of this study is to examine glucocorticoid signaling as a potential mechanism for differential gene expression. Genes potentially regulated by glucocorticoids and that serve relevant neural functions (see Discussion section below) for learning to cope modeled in monkeys were then assessed in mice.…”