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Schizophr Res. 2018 Feb;192:423-430. doi: 10.1016/j.schres.2017.04.014. Epub 2017 Apr 20.

Changes in the expression of metabotropic glutamate receptor 5 (mGluR5) in a ketamine-based animal model of schizophrenia.

Author information

1
Institute of Pharmacology, Polish Academy of Sciences, Department of Pharmacology, 31-343 Krakow, Smetna Street 12, Poland. Electronic address: zurawek@if-pan.krakow.pl.
2
Institute of Pharmacology, Polish Academy of Sciences, Department of Pharmacology, 31-343 Krakow, Smetna Street 12, Poland.
3
Institute of Pharmacology, Polish Academy of Sciences, Department of Behavioural Neuroscience and Drug Development, 31-343 Krakow, Smetna Street 12, Poland.
4
Faculty of Health Sciences, Collegium Medicum, Jagiellonian University, Krakow, Poland.

Abstract

It has been shown that the metabotropic glutamate receptor subtype 5 (mGluR5) is functionally associated with the NMDA subtype of the glutamate receptor family (NMDA receptors). These two receptors colocalize in brain regions associated with schizophrenia. Although the role of the NMDA receptor in cognitive and negative symptoms of schizophrenia is well studied, information about the role of mGluR5 receptors in schizophrenia is sparse. In our work, we show that subchronic administration of ketamine, a well-studied, non-competitive antagonist of NMDA receptors, caused cognitive deficits in rats as shown by testing novel object recognition (NOR). Moreover, we reveal that subchronic administration of ketamine increased the mRNA and protein expression levels of mGluR5 receptors in regions CA1 and CA3 of the dorsal part of the hippocampus, both of which are strongly associated with the formation of visual memory, which is tested via NOR. We postulate that increased expression of mGluR5 receptors in the dorsal part of the hippocampus may reflect compensatory changes to imbalanced glutamate neurotransmission associated with the hypoactivation of NMDA receptors.

KEYWORDS:

Autoradiography; In situ hybridization; Ketamine; Metabotropic glutamate receptor subtype 5; Novel object recognition; Schizophrenia

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