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Open Access

Long-term depression-like effect of a single immune challenge in neuropeptide Y Y2 and Y4 receptor knockout mice

  • Evelin Painsipp1Email author,
  • Herbert Herzog2,
  • Günther Sperk3 and
  • Peter Holzer1
BMC Pharmacology20088(Suppl 1):A39

Published: 5 November 2008

Background and aims

Deletion of neuropeptide Y (NPY) Y2 and Y4 receptors reduces anxiety-like and depression-related behaviour [1]. We have previously found that Y2 receptor knockout (Y2-/-) mice are particularly sensitive to the short-term anxiogenic effect of immune stress evoked by systemic lipopolysaccharide (LPS) [2]. In the present study we investigated whether LPS challenge has long-term effects on anxiety-like and depression-related behaviour and whether these effects are altered in Y2-/- and Y4-/- mice.

Materials and methods

Adult control and germline Y2-/- and Y4-/- mice were used. Anxiety-like behaviour was assessed on the elevated plus maze, and depression-related behaviour was estimated with the forced swim test. These tests were carried out 1 day or 4 weeks after a single intraperitoneal injection of LPS (0.83 mg/kg) or vehicle (sterile saline).


Relative to control animals, vehicle-treated Y2-/- and Y4-/- mice were less anxious and displayed reduced depression-like behaviour. One day after LPS injection, anxiety-like behaviour remained unaltered in control animals but was markedly enhanced in Y2-/- and Y4-/- mice. Four weeks post-treatment, the anxiogenic effect of LPS was still seen in Y4-/- mice but had gone in control and Y2-/- mice. Depression-related behaviour was enhanced 1 day after LPS treatment in control and Y2-/- mice, but not in Y4-/- mice. Four weeks post-treatment, the effect of LPS challenge to increase depression-like behaviour had waned in control mice, but was still present in Y2-/- mice and was first observed in Y4-/- mice.


Y2-/- and Y4-/- mice are particularly susceptible to the effects of immune stress to cause a long-term enhancement of anxiety- and depression-like behaviour. With Y2 and Y4 receptors playing distinct roles in these persistent alterations of emotional-affective behaviour, it is emerging that endogenous NPY has an important bearing on immune signalling to the brain.



This study was supported by the Zukunftsfonds Steiermark (grant 262) and the Austrian Scientific Research Funds (FWF grant L25-B05).

Authors’ Affiliations

Research Unit of Translational Neurogastroenterology, Institute of Experimental and Clinical Pharmacology, Medical University of Graz
Neurobiology Research Program, Garvan Institute of Medical Research
Department of Pharmacology, Medical University of Innsbruck


  1. Painsipp E, Wultsch T, Edelsbrunner ME, Tasan RO, Singewald N, Herzog H, Holzer P: Reduced anxiety-like and depression-related behavior in neuropeptide Y Y4 receptor knockout mice. Genes Brain Behav. 2008, 7: 532-542. 10.1111/j.1601-183X.2008.00389.x.PubMed CentralView ArticlePubMedGoogle Scholar
  2. Painsipp E, Herzog H, Holzer P: Implication of neuropeptide-Y Y2 receptors in the effects of immune stress on emotional, locomotor and social behavior of mice. Neuropharmacology. 2008, 55: 117-126. 10.1016/j.neuropharm.2008.05.004.PubMed CentralView ArticlePubMedGoogle Scholar


© Painsipp et al; licensee BioMed Central Ltd. 2008

This article is published under license to BioMed Central Ltd.