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Evidence from knockout mice that neuropeptide-Y Y2 and Y4 receptor signalling prevents long-term depression-like behaviour caused by immune challenge


Neuropeptide Y participates in the acute behavioural responses to immune challenge, since Y2 receptor knockout (Y2/) mice are particularly sensitive to the short-term anxiogenic-like effect of bacterial lipopolysaccharide. The present exploratory study addressed the involvement of Y2 and Y4 receptors in the long-term behavioural responses to immune challenge. A single intraperitoneal injection of lipopolysaccharide (0.83 mg/kg) to control mice did not affect open field behaviour 3 h post-treatment but enhanced anxiety-like behaviour in Y2/ as well as Y4/ mice. Four weeks post-treatment this behavioural effect of lipopolysaccharide persisted in Y4/ mice but had gone in Y2/ mice. Depression-related behaviour in the forced swim test was enhanced 1 day post-lipopolysaccharide in control and Y2/ mice, but not in Y4/ mice. Four weeks post-treatment, the depressogenic-like effect of lipopolysaccharide had waned in control mice, persisted in Y2/ mice and was first observed in Y4/ mice. In summary, knockout of Y2 and/or Y4 receptors unmasks the ability of a single lipopolysaccharide injection to cause a delayed and prolonged increase in anxiety- and/or depression-like behaviour. These findings suggest that neuropeptide Y acting via Y2 and Y4 receptors prevents the development of long-term anxiety- and depression-like behaviour caused by acute immune challenge.

Type Journal
ISBN 1461-7285 (Electronic) 0269-8811 (Linking)
Authors Painsipp, E.; Herzog, H.; Holzer, P.;
Garvan Authors Prof Herbert Herzog
Published Date 2010-01-01 00:00:00
Published Volume 24
Published Issue 10
Published Pages 1551-60
Status Published In-print