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

Acta Neuropsychiatr. 2015 Jun;27(3):189-94. doi: 10.1017/neu.2015.4. Epub 2015 Feb 20.


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 system; depression; neuroendocrinology; psychoneuroimmunology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal / drug effects*
  • Body Weight / drug effects
  • Cytokines / metabolism
  • Depression / chemically induced*
  • Depression / diagnosis
  • Depression / metabolism
  • Depression / psychology
  • Disease Models, Animal
  • Frontal Lobe / drug effects
  • Frontal Lobe / metabolism
  • Glucose / metabolism
  • Glucose Tolerance Test / methods
  • Insulin / metabolism
  • Lipopolysaccharides / administration & dosage*
  • Male
  • Motor Activity / drug effects
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley


  • Cytokines
  • Insulin
  • Lipopolysaccharides
  • Glucose