Chronic sensory contact with subordinated conspecifics promotes splenic glucocorticoid resistance in experimentally wounded C57BL/6N male mice

TL;DR

Mice exposed to chronic social stress and a specific type of wound show reduced spleen response to stress hormones.

Contribution

A new bite wound-independent method to induce splenic glucocorticoid resistance in mice is proposed.

Findings

Individually-housed mice with sensory contact to social defeat show mild splenic glucocorticoid resistance.

Standardized i.p.-wounding combined with chronic sensory stress induces functional splenic GC resistance.

This method avoids the need for uncontrollable bite wounds in stress models.

Abstract

Chronic psychosocial stress induced by the chronic subordinate colony housing (CSC, 19 Days) paradigm promotes functional splenic in vitro glucocorticoid (GC) resistance, but only if associated with significant bite wounding or prior abdominal transmitter implantation. Moreover, sensory contact to social defeat of conspecifics represents a social stressor for the observer individual. As the occurence and severity of bite wounding is not adequately controllable, the present study aimed to develop an animal model, allowing a bite wound-independent, more reliable generation of chronically-stressed mice characterized by functional splenic in vitro GC resistance. Therefore, male C57BL/6N mice received a standardized sterile intraperitoneal (i.p.) incision surgery or SHAM treatment one week prior to 19-days of (i) CSC, (ii) witnessing social defeat during CSC exposure in sensory contact (SENS) or (iii) single-housing for control (SHC), before assessing basal and LPS-induced splenic in vitro cell viability and GC resistance. Our results indicate that individually-housed SENS but not CSC mice develop mild signs of splenic in vitro GC resistance, when undergoing prior i.p.-wounding. Taken together and considering that future studies are warranted, our findings support the hypothesis that the combination of repeated standardized i.p.-wounding with chronic sensory stress exposure represents an adequate tool to induce functional splenic in vitro GC resistance independent of the occurrence of uncontrollable bite wounds required in social stress paradigms to induce a comparable phenotype.

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