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The effect of mGlu(8) deficiency in animal models of psychiatric diseases

Fendt, Markus and Buerki, Hugo and Imobersteg, Stefan and Van Der Putten, P. Herman and Mcallister, Kevin and Leslie, Julian and Shaw, David and Hölscher, Christian (2009) The effect of mGlu(8) deficiency in animal models of psychiatric diseases. Genes, Brain, and Behavior, 9 (1). pp. 33-44. ISSN 1601-1848

Abstract

The metabotropic glutamate receptor subtype 8 (mGlu(8)) is presynaptically located and regulates the release of the transmitter. Dysfunctions of this mechanism are involved in the pathophysiology of different psychiatric disorders. mGlu(8) deficient mice have been previously investigated in a range of studies, but the results are contradictory and there are still many open questions. Therefore, we tested mGlu(8)-deficient animals in different behavioral tasks that are commonly used in neuropsychiatric research. Our results show a robust contextual fear deficit in mGlu(8)-deficient mice. Furthermore, novel object recognition, chlordiazepoxide-facilitated extinction of operant conditioning and the acoustic startle response were attenuated by mGlu(8) deficiency. We found no changes in sensory processing, locomotor activity, prepulse inhibition, phencyclidine-induced changes in locomotion or prepulse inhibition, operant conditioning, conditioned fear to a discrete cue or in animal models of innate fear and post-traumatic stress disorder. We conclude that mGlu(8) might be a potential target for disorders with pathophysiological changes in brain areas where mGlu(8) modulates glutamate and gamma-amino butyric acid (GABA) transmission. Our data especially point to anxiety disorders involving exaggerated contextual fear, such as generalized anxiety disorders, and to conditions with disturbed declarative memory.

Item Type: Article
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Additional Information: Archiving not allowed on institutional repository
Keywords: Anxiety; conditioned fear; context; extinction; freezing; instrumental learning; object recognition; prepulse inhibition; startle
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Date Deposited: 13 Oct 2015 13:16
Last Modified: 13 Oct 2015 13:16
URI: https://oak.novartis.com/id/eprint/2083

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