The effect of mGlu(8) deficiency in animal models of psychiatric diseases
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Fendt, Markus, Buerki, Hugo, Imobersteg, Stefan, Van Der Putten, P. Herman, Mcallister, Kevin, Leslie, Julian, 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 |