Effects of chronic MK-801 treatment on the relative mRNA expression of NMDA receptor subunits and splice variants in a pharmacological model for psychosis

The NMDA receptor antagonists PCP and ketamine can induce psychotomimetic effects in healthy humans. Thus, our and others groups developed animal models for schizophrenia based on altered glutamatergic neurotransmission. Findings in our animal model of low chronic treatment with MK-801 showed parallels to schizophrenia on molecular, cellular, functional and behavioural levels. In this study, examines the relative mRNA expression of insertion or skipping of NR1 exon 5 which encodes a 21 amino acid sequence in the N-terminus domain, the relative amount of NR2C / NR2A as well as the ratio of GAPDH (a constitutional expressed housekeeping gene) / NR2B. Transcripts coding for NR2B and the NR1 exon 5 insertion were increased whereas NR2A was decreased in the hippocampus. Changes in the same direction were observed for NR2A and NR2B in the frontal cortex, for NR2A in the occipital cortex, and for the NR1 exon 5 insertion in the striatum. We conclude that chronic low-dose treatment with the NMDA receptor antagonist MK-801 alters the expression of NMDA receptor subunits.