Volume 8 Supplement 1

14th Scientific Symposium of the Austrian Pharmacological Society (APHAR)

Open Access

Increased novelty-induced motor activity and reduced depression-like behavior in NPY Y4 receptor knockout mice

  • Ramon O Tasan1Email author,
  • Shu Lin2,
  • Alfred Hetzenauer3,
  • Nicolas Singewald3,
  • Herbert Herzog2 and
  • Günther Sperk1
BMC Pharmacology20088(Suppl 1):A17

https://doi.org/10.1186/1471-2210-8-S1-A17

Published: 5 November 2008

There is growing evidence that neuropeptide Y acting through Y1 and Y2 receptors has a prominent role in modulating anxiety- and depression-like behavior in rodents. However, a role of other Y receptors like that of Y4 receptors in this process is poorly understood. We now investigated male Y2, Y4 single and Y2/Y4 double knockout mice in behavioral paradigms for changes in motor activity, anxiety and depression-like behavior. Y4 and Y2 knockout mice revealed an anxiolytic phenotype in the light/dark test, marble-burying test and motor-activity independent in stress-induced hyperthermia, and reduced depression-like behavior in the forced swim and tail suspension tests. In Y2/Y4 double knockout mice, the response in the light/dark test and in the forced swim test was further enhanced compared to Y4 and Y2 knockout mice, respectively. Motor activity was increased in Y2, Y4 and Y2/Y4 knockout mice under changing and stressful conditions, but not altered in a familiar environment. High levels of Y4 binding sites were observed in brain stem nuclei including nucleus of solitary tract and area postrema. Lower levels were found in the medial amygdala and hypothalamus. Peripheral administration of PP induced Y4 receptor-dependent c-Fos expression in brain stem, hypothalamus and amygdala. PP released peripherally from the pancreas in response to food intake, may act not only as a satiety signal but also modulate anxiety-related locomotion. Lack of central Y4 receptors appears to be responsible for the alterations in behavior seen in Y4 and Y2/Y4 knockout mice suggesting a potential new target to treat anxiety-related disorders.

Declarations

Acknowledgements

Funded by the Austrian Science Funds project S102.

Authors’ Affiliations

(1)
Department of Pharmacology, Medical University of Innsbruck
(2)
Neuroscience Research Program, Garvan Institute of Medical Research
(3)
Department of Pharmacology and Toxicology, Institute of Pharmacy and Center of Molecular Biosciences Innsbruck (CMBI), University of Innsbruck

Copyright

© Tasan et al; licensee BioMed Central Ltd. 2008

This article is published under license to BioMed Central Ltd.

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