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

Published online by Cambridge University Press:  20 February 2015

Christina Weide Fischer ,
Nico Liebenberg Open the ORCID record for Nico Liebenberg [Opens in a new window] ,
Anne Mette Madsen ,
Heidi Kaastrup Müller ,
Sten Lund  and
Gregers Wegener
Christina Weide Fischer*
Affiliation:
Translational Neuropsychiatry Unit, Aarhus University, Risskov, Denmark
Nico Liebenberg
Affiliation:
Translational Neuropsychiatry Unit, Aarhus University, Risskov, Denmark
Anne Mette Madsen
Affiliation:
The National Research Centre for the Working Environment, Copenhagen, Denmark
Heidi Kaastrup Müller
Affiliation:
Translational Neuropsychiatry Unit, Aarhus University, Risskov, Denmark
Sten Lund
Affiliation:
Medical Research Laboratory, Medical Department M (Endocrinology and Diabetes), Aarhus University Hospital, Denmark
Gregers Wegener
Affiliation:
Translational Neuropsychiatry Unit, Aarhus University, Risskov, Denmark
*
Christina Weide Fischer, Translational Neuropsychiatry Unit, Aarhus University, Skovagervej 2, 8240 Risskov, Denmark. Tel: +457 847 1122; Fax: +45 8471124; E-mail: [email protected]
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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.

Keywords

central nervous systemdepressionneuroendocrinologypsychoneuroimmunology
Type
Short Communication
Information
Acta Neuropsychiatrica , Volume 27 , Issue 3 , June 2015 , pp. 189 - 194
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Copyright
© Scandinavian College of Neuropsychopharmacology 2015 

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References

1.Maes, M. Evidence for an immune response in major depression: a review and hypothesis. Prog Neuropsychopharmacol Biol Psychiatry 1995;19:11–38.CrossRefGoogle ScholarPubMed
2.Gregor, MF, Hotamisligil, GS. Inflammatory mechanisms in obesity. Annu Rev Immunol 2011;29:415–445.CrossRefGoogle ScholarPubMed
3.Wellen, KE, Hotamisligil, GS. Inflammation, stress, and diabetes. J Clin Invest 2005;115:1111–1119.CrossRefGoogle ScholarPubMed
4.Stuart, MJ, Baune, BT. Depression and type 2 diabetes: inflammatory mechanisms of a psychoneuroendocrine co-morbidity. Neurosci Biobehav Rev 2012;36:658–676.CrossRefGoogle ScholarPubMed
5.Mezuk, Bet al. Depression and type 2 diabetes over the lifespan: a meta-analysis. Diabetes Care 2008;31:2383–2390.CrossRefGoogle ScholarPubMed
6.Rotella, F, Mannucci, E. Diabetes mellitus as a risk factor for depression. A meta-analysis of longitudinal studies. Diabetes Res Clin Pract 2013;99:98–104.CrossRefGoogle ScholarPubMed
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;83:847–850.Google ScholarPubMed
8.Shoelson, SE, Herrero, L, Naaz, A. Obesity, inflammation, and insulin resistance. Gastroenterology 2007;132:2169–2180.CrossRefGoogle ScholarPubMed
9.Plata-Salaman, CR. Immunomodulators and feeding regulation: a humoral link between the immune and nervous systems. Brain Behav Immun 1989;3:193–213.CrossRefGoogle ScholarPubMed
10.Hotamisligil, GS, Shargill, NS, Spiegelman, BM. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science 1993;259:87–91.CrossRefGoogle ScholarPubMed
11.Dowlati, Yet al. A meta-analysis of cytokines in major depression. Biol Psychiatry 2010;67:446–457.CrossRefGoogle ScholarPubMed
12.Capuron, L, Miller, AH. Immune system to brain signaling: neuropsychopharmacological implications. Pharmacol Ther 2011;130:226–238.CrossRefGoogle ScholarPubMed
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;31:96–104.CrossRefGoogle ScholarPubMed
14.Puntener, Uet al. Long-term impact of systemic bacterial infection on the cerebral vasculature and microglia. J Neuroinflammation 2012;9:146.CrossRefGoogle ScholarPubMed
15.Cani, PDet al. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes 2007;56:1761–1772.CrossRefGoogle ScholarPubMed
16.Porsolt, RD, Le Pichon, M, Jalfre, M. Depression: a new animal model sensitive to antidepressant treatments. Nature 1977;266:730–732.CrossRefGoogle ScholarPubMed
17.Cryan, JF, Markou, A, Lucki, I. Assessing antidepressant activity in rodents: recent developments and future needs. Trends Pharmacol Sci 2002;23:238–245.CrossRefGoogle ScholarPubMed
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;57:289–300.Google Scholar
19.Dantzer, R. Cytokine, sickness behavior, and depression. Immunol Allergy Clin North Am 2009;29:247–264.CrossRefGoogle ScholarPubMed
20.Haley, PJ. Species differences in the structure and function of the immune system. Toxicology 2003;188:49–71.CrossRefGoogle ScholarPubMed
21.Grossman, C. Possible underlying mechanisms of sexual dimorphism in the immune response, fact and hypothesis. J Steroid Biochem 1989;34:241–251.CrossRefGoogle ScholarPubMed
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;111:104–115.CrossRefGoogle Scholar