Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 6 (6), e20719

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

Affiliations

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

Evelin Painsipp et al. PLoS One.

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.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Experimental groups and time lines.
In protocol 1, the effect of IP injected vehicle (VEH) and LPS on depression-like behavior in the FST was assessed 1 and 28 days post-injection. In protocol 2, the depression-related effect of vehicle and LPS was assessed with the sucrose preference (SP) test during days −1–4 and days 26–27 post-injection.
Figure 2
Figure 2. Effect of LPS (0.83 mg/kg injected IP), relative to vehicle (VEH), on the body weight of CD1 mice as measured immediately before and 1 day (A) as well as 28 days (B) after treatment under single and group housing conditions.
The graphs show the change in weight (weight after treatment minus weight before treatment). The values are means+SEM, n = 8. *** P<0.01 versus change in weight following treatment with vehicle.
Figure 3
Figure 3. Effect of LPS (0.83 mg/kg injected IP), relative to vehicle (VEH), on the body weight of C57BL/6 mice as measured immediately before and 1 day (A) as well as 28 days (B) after treatment under single and group housing conditions.
The graphs show the change in weight (weight after treatment minus weight before treatment). The values are means+SEM, n = 7–8. *** P<0.01 versus change in weight following treatment with vehicle.
Figure 4
Figure 4. Effect of LPS (0.83 mg/kg injected IP), relative to vehicle (VEH), on the behavior of CD1 mice in the FST as recorded 1 and 28 days after treatment under single and group housing conditions.
The graphs show (A) the duration of immobility, (B) the duration of swimming, and (C) the duration of climbing, these parameters being expressed as a percentage of the total test duration. The values are means+SEM, n = 8. * P≤0.1, *** P<0.01 versus vehicle-treated mice at the same time point post-treatment. In panel B (Single) it was not possible to apply a post-hoc test because two-way ANOVA failed to disclose any interaction between the factors time and treatment.
Figure 5
Figure 5. Effect of LPS (0.83 mg/kg injected IP), relative to vehicle (VEH), on the behavior of C57BL/6 mice in the FST as recorded 1 and 28 days after treatment under single and group housing conditions.
The graphs show (A) the duration of immobility, (B) the duration of swimming, and (C) the duration of climbing, these parameters being expressed as a percentage of the total test duration. The values are means+SEM, n = 8. ** P<0.05, *** P<0.01 versus vehicle-treated mice at the same time point post-treatment, ++ P<0.05, +++ P<0.01 versus vehicle-treated mice tested 28 days post-treatment. In panels A (Single), B (Single) and C (Single) it was not possible to apply a post-hoc test because two-way ANOVA failed to disclose any interaction between the factors time and treatment.
Figure 6
Figure 6. Effect of LPS (0.83 mg/kg injected IP), relative to vehicle (VEH), on plasma concentrations of corticosterone as recorded 1 and 28 days after treatment under single and group housing conditions.
Trunk blood of CD1 (A) and C57BL/6 (B) mice for the corticosterone assay was taken 30 min after the FST had been started. The values are means+SEM, n = 7–8. *** P<0.01 versus vehicle-treated mice at the same time point post-treatment, + P≤0.1, +++ P<0.01 versus vehicle-treated mice tested 1 day post-treatment. In panel A it was not possible to apply a post-hoc test because two-way ANOVA failed to disclose any interaction between the factors time and treatment.
Figure 7
Figure 7. Effect of LPS (0.83 mg/kg injected IP), relative to vehicle (VEH), on plasma concentrations of interleukin-6 as recorded 1 and 28 days after treatment under single and group housing conditions.
Trunk blood of CD1 (A) and C57BL/6 (B) mice for the interleukin-6 assay was taken 30 min after the FST had been started. The values are means+SEM, n = 7–8. ** P<0.05, *** P<0.01 versus vehicle-treated mice at the same time point post-treatment.
Figure 8
Figure 8. Effect of (A) vehicle (VEH) and (B) LPS (0.83 mg/kg injected IP) on the daily consumption of sucrose (1%) solution and normal tap water in singly housed C57BL/6 mice.
The main graphs show the absolute daily intake of sucrose solution and water (ml). In the inserts, the daily intake of sucrose solution and water on the day before treatment (day -1) and on day 26 post-treatment is expressed as a percentage of the total daily fluid intake. The values are means±SEM, n = 7. *** P<0.01 versus water intake.
Figure 9
Figure 9. Effect of vehicle (VEH) and LPS (0.83 mg/kg injected IP) on the total daily intake of fluid in singly housed C57BL/6 mice.
The graph shows the absolute daily intake of fluid on the day before treatment (day -1) and on days 1, 2 and 26 post-treatment. The values are means+SEM, n = 7. ** P<0.05, *** P<0.01 versus vehicle on the same day, +++ P<0.01 versus vehicle on all other days.

Similar articles

See all similar articles

Cited by 23 PubMed Central articles

See all "Cited by" articles

References

    1. Maes M, Smith R, Scharpe S. The monocyte-T-lymphocyte hypothesis of major depression. Psychoneuroendocrinology. 1995;20:111–116. - PubMed
    1. Maes M, Yirmyia R, Noraberg J, Brene S, Hibbeln J, et al. The inflammatory & neurodegenerative (I&ND) hypothesis of depression: leads for future research and new drug developments in depression. Metab Brain Dis. 2009;24:27–53. - PubMed
    1. Yirmiya R. Endotoxin produces a depressive-like episode in rats. Brain Res. 1996;711:163–174. - PubMed
    1. Yirmiya R. The inflammatory nature of depression. Front Neurosci. 2009;3:262.
    1. Raison CL, Capuron L, Miller AH. Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends Immunol. 2006;27:24–31. - PMC - PubMed

Publication types

MeSH terms

Feedback