Long-term depression-like effect of a single immune challenge in neuropeptide Y Y2 and Y4 receptor knockout mice
© Painsipp et al; licensee BioMed Central Ltd. 2008
Published: 5 November 2008
Background and aims
Deletion of neuropeptide Y (NPY) Y2 and Y4 receptors reduces anxiety-like and depression-related behaviour . 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) . 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).
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