Prolonged Depression-Like Behavior Caused by Immune Challenge: Influence of Mouse Strain and Social Environment

Evelin Painsipp,Frank Sinner,Peter Holzer,Martin J Köfer,Andreas Reif

doi:10.1371/journal.pone.0020719

Evelin Painsipp, Frank Sinner + Show 3 more

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https://doi.org/10.1371/journal.pone.0020719

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Abstract

Immune challenge by bacterial lipopolysaccharide (LPS) causes short-term behavioral changes indicative of depression. The present study sought to explore whether LPS is able to induce long-term changes in depression-related behavior and whether such an effect depends on mouse strain and social context. LPS (0.83 mg/kg) or vehicle was administered intraperitoneally to female CD1 and C57BL/6 mice that were housed singly or in groups of 4. Depression-like behavior was assessed with the forced swim test (FST) 1 and 28 days post-treatment. Group-housed CD1 mice exhibited depression-like behavior 1 day post-LPS, an effect that leveled off during the subsequent 28 days, while the behavior of singly housed CD1 mice was little affected. In contrast, singly housed C57BL/6 mice responded to LPS with an increase in depression-like behavior that was maintained for 4 weeks post-treatment and confirmed by the sucrose preference test. Group-housed C57BL/6 mice likewise displayed an increased depression-like behavior 4 weeks post-treatment. The behavioral changes induced by LPS in C57BL/6 mice were associated with a particularly pronounced rise of interleukin-6 in blood plasma within 1 day post-treatment and with changes in the dynamics of the corticosterone response to the FST. The current data demonstrate that immune challenge with LPS is able to induce prolonged depression-like behavior, an effect that depends on genetic background (strain). The discovery of an experimental model of long-term depression-like behavior after acute immune challenge is of relevance to the analysis of the epigenetic and pathophysiologic mechanisms of immune system-related affective disorders.

Highlights

Experimental and clinical evidence indicates that activation of the immune system contributes to the pathogenesis of mood disorders [1,2,3,4,5,6]
When neuropeptide Y receptors of subtype Y2 or Y4 have been knocked out, depression-like behavior is seen even 4 weeks after a single injection of low-dose LPS [14]. This observation led us to hypothesize that, depending on genetic background and social context, intraperitoneal (IP) injection of LPS is able to induce long-term depressionlike behavior. We addressed this hypothesis by studying the behavioral effect of LPS with the forced swim test (FST), a measure of behavioral despair [15], and the sucrose preference test, a measure of depression-related anhedonia [12]
The current study demonstrates that immune challenge with

Summary

Introduction

Experimental and clinical evidence indicates that activation of the immune system contributes to the pathogenesis of mood disorders [1,2,3,4,5,6]. When neuropeptide Y receptors of subtype Y2 or Y4 have been knocked out, depression-like behavior is seen even 4 weeks after a single injection of low-dose LPS [14] This observation led us to hypothesize that, depending on genetic background (mouse strain) and social context (single versus group housing), intraperitoneal (IP) injection of LPS is able to induce long-term depressionlike behavior. We addressed this hypothesis by studying the behavioral effect of LPS with the forced swim test (FST), a measure of behavioral despair [15], and the sucrose preference test, a measure of depression-related anhedonia [12]. These tests were carried out 1 day and 4 weeks post-LPS treatment

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