Acoustic startle response and sensorimotor gating in a genetic mouse model for the Y1 receptor

Karl, T.; Chesworth, R.; Duffy, L.; Herzog, H.

doi:10.1016/j.npep.2009.12.008

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Volume 44, Issue 3 , Pages 233-239, June 2010

Acoustic startle response and sensorimotor gating in a genetic mouse model for the Y₁ receptor

T. Karl
- Neuroscience Research Program, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia
- Schizophrenia Research Institute (SRI), Sydney, NSW 2010, Australia
- Prince of Wales Medical Research Institute, Sydney, NSW 2031, Australia
- Corresponding author. Address: Prince of Wales Medical Research Institute, Corner Barker Street and Easy Street, Randwick (Sydney), NSW 2031, Australia. Tel./fax: +61 2 9399 1005.
- Authors contributed equally to this work.
R. Chesworth
- Neuroscience Research Program, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia
- Schizophrenia Research Institute (SRI), Sydney, NSW 2010, Australia
- Prince of Wales Medical Research Institute, Sydney, NSW 2031, Australia
- Authors contributed equally to this work.
L. Duffy
- Neuroscience Research Program, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia
- Schizophrenia Research Institute (SRI), Sydney, NSW 2010, Australia
H. Herzog
- Neuroscience Research Program, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia

Received 30 June 2009; accepted 11 December 2009. published online 25 January 2010.

Abstract

Recent research has highlighted a potential role for neuropeptide Y (NPY) and its Y₁ receptor in the development of schizophrenia. Genetic as well as molecular biological studies have demonstrated reduced levels of NPY in schizophrenia patients. Importantly, Y₁ receptors may mediate some of the potential effects of NPY on schizophrenia, as decreased Y₁ receptor expression has been found in the lymphocytes of schizophrenia patients. To clarify NPY’s role in schizophrenia, we investigated a genetic animal model for Y₁ deficiency in regard to (i) acoustic startle response (ASR), (ii) habituation to ASR and (iii) sensorimotor gating [i.e. prepulse inhibition (PPI)] using two different PPI protocols. Mutant and wild type-like mice were screened for baseline behaviours and after pharmacological challenge with the psychotropic drugs dexamphetamine (DEX) and MK-801. Y₁ knockout mice (Y₁^−/−) showed a moderate reduction of the ASR and an impaired ASR habituation at baseline and after DEX treatment. The baseline PPI performance of Y₁ mutant mice was unaltered their response to DEX and MK-801 challenge was moderately different compared to control mice, which was dependent on the PPI protocol used. MK-801 challenge had a protocol-dependent differential effect in Y₁^−/− mice and DEX a more pronounced impact at the highest prepulse intensities. In conclusion, it appears that the Y₁ receptor influences the acoustic startle response and its habituation but does not play a major role in sensorimotor gating. Further explorations into the effects of Y₁ deficiency seem valid.