Skip to main content Accessibility help
×
Home

Chronic lipopolysaccharide infusion fails to induce depressive-like behaviour in adult male rats

  • Christina Weide Fischer (a1), Nico Liebenberg (a1), Anne Mette Madsen (a2), Heidi Kaastrup Müller (a1), Sten Lund (a3) and Gregers Wegener (a1)...

Abstract

Background

Chronic inflammation is implicated in numerous diseases, including major depression and type 2 diabetes mellitus (T2DM). Since depression and T2DM often co-exist, inflammatory pathways are suggested as a possible link. Hence, the establishment of an immune-mediated animal model would shed light on mechanisms possibly linking depression and metabolic alterations.

Objective

In this study we investigated a behavioural and metabolic paradigm following chronic infusion with low doses of lipopolysaccharide (LPS) using osmotic minipumps in male rats.

Methods

Behavioural testing consisted of evaluating activity level in the open field and depressive-like behaviour in the forced swim test. Metabolic assessment included measurement of body weight, food and water intake, and glucose and insulin levels during an oral glucose tolerance test.

Results

LPS-infused rats showed acute signs of sickness behaviour, but chronic LPS infusion did not induce behavioural or metabolic changes.

Conclusion

These results suggest that although inflammation is immediately induced as indicated by acute sickness, 4 weeks of chronic LPS administration via osmotic minipumps did not result in behavioural changes. Therefore, this paradigm may not be a suitable model for studying the underlying mechanisms that link depression and T2DM.

Copyright

Corresponding author

Christina Weide Fischer, Translational Neuropsychiatry Unit, Aarhus University, Skovagervej 2, 8240 Risskov, Denmark. Tel: +457 847 1122; Fax: +45 8471124; E-mail: Christina.weide.fischer@clin.au.dk

References

Hide All
1.Maes, M. Evidence for an immune response in major depression: a review and hypothesis. Prog Neuropsychopharmacol Biol Psychiatry 1995;19:1138.
2.Gregor, MF, Hotamisligil, GS. Inflammatory mechanisms in obesity. Annu Rev Immunol 2011;29:415445.
3.Wellen, KE, Hotamisligil, GS. Inflammation, stress, and diabetes. J Clin Invest 2005;115:11111119.
4.Stuart, MJ, Baune, BT. Depression and type 2 diabetes: inflammatory mechanisms of a psychoneuroendocrine co-morbidity. Neurosci Biobehav Rev 2012;36:658676.
5.Mezuk, Bet al. Depression and type 2 diabetes over the lifespan: a meta-analysis. Diabetes Care 2008;31:23832390.
6.Rotella, F, Mannucci, E. Diabetes mellitus as a risk factor for depression. A meta-analysis of longitudinal studies. Diabetes Res Clin Pract 2013;99:98104.
7.Fried, SK, Bunkin, DA, Greenberg, AS. Omental and subcutaneous adipose tissues of obese subjects release interleukin-6: depot difference and regulation by glucocorticoid. J Clin Endocrinol Metab 1998;83:847850.
8.Shoelson, SE, Herrero, L, Naaz, A. Obesity, inflammation, and insulin resistance. Gastroenterology 2007;132:21692180.
9.Plata-Salaman, CR. Immunomodulators and feeding regulation: a humoral link between the immune and nervous systems. Brain Behav Immun 1989;3:193213.
10.Hotamisligil, GS, Shargill, NS, Spiegelman, BM. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science 1993;259:8791.
11.Dowlati, Yet al. A meta-analysis of cytokines in major depression. Biol Psychiatry 2010;67:446457.
12.Capuron, L, Miller, AH. Immune system to brain signaling: neuropsychopharmacological implications. Pharmacol Ther 2011;130:226238.
13.Kubera, Met al. A new animal model of (chronic) depression induced by repeated and intermittent lipopolysaccharide administration for 4 months. Brain Behav Immun 2013;31:96104.
14.Puntener, Uet al. Long-term impact of systemic bacterial infection on the cerebral vasculature and microglia. J Neuroinflammation 2012;9:146.
15.Cani, PDet al. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes 2007;56:17611772.
16.Porsolt, RD, Le Pichon, M, Jalfre, M. Depression: a new animal model sensitive to antidepressant treatments. Nature 1977;266:730732.
17.Cryan, JF, Markou, A, Lucki, I. Assessing antidepressant activity in rodents: recent developments and future needs. Trends Pharmacol Sci 2002;23:238245.
18.Benjamini, Y, Hochberg, Y. Controlling the false discovery rate – a practical and powerful approach to multiple testing. J R Statist Soc B-Methodological 1995;57:289300.
19.Dantzer, R. Cytokine, sickness behavior, and depression. Immunol Allergy Clin North Am 2009;29:247264.
20.Haley, PJ. Species differences in the structure and function of the immune system. Toxicology 2003;188:4971.
21.Grossman, C. Possible underlying mechanisms of sexual dimorphism in the immune response, fact and hypothesis. J Steroid Biochem 1989;34:241251.
22.Kehl, LJ, Kovacs, KJ, Larson, AA. Tolerance develops to the effect of lipopolysaccharides on movement-evoked hyperalgesia when administered chronically by a systemic but not an intrathecal route. Pain 2004;111:104115.

Keywords

Chronic lipopolysaccharide infusion fails to induce depressive-like behaviour in adult male rats

  • Christina Weide Fischer (a1), Nico Liebenberg (a1), Anne Mette Madsen (a2), Heidi Kaastrup Müller (a1), Sten Lund (a3) and Gregers Wegener (a1)...

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed