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.
Painsipp
Evelin
E
Research Unit of Translational Neurogastroenterology, Institute of Experimental and Clinical Pharmacology, Medical University of Graz, Graz, Austria.
Herzog
Herbert
H
Holzer
Peter
P
D000818:Animals; D001007:Anxiety; D001522:Behavior, Animal; D003863:Depression; D005106:Exploratory Behavior; D005260:Female; D007155:Immunologic Factors / Q000633:toxicity; D008070:Lipopolysaccharides / Q000633:toxicity; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009478:Neuropeptide Y / Q000502:physiology*; D017476:Receptors, Neuropeptide Y / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D013312:Stress, Physiological / Q000276:immunology*; D013550:Swimming; D013997:Time Factors
D007155:Immunologic Factors; D008070:Lipopolysaccharides; D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; C095889:neuropeptide Y2 receptor; C109491:neuropeptide Y4 receptor