The psychotomimetic properties of NMDA glutamate receptor antagonists suggest there may be disease related changes of this receptor in schizophrenia. Using in situ hybridisation histochemistry (ISHH), we measured mRNA for the obligatory NMDAR1 subunit of the NMDA glutamate receptor in post-mortem samples of hippocampus from schizophrenics, depressives, bipolar patients and normal controls. A significant main effect of diagnosis was observed in the dentate gyrus (ANOVA, p = 0.004) and a trend in the CA3 region (ANOVA, p = 0.06), with all psychiatric groups having reduced NMDAR1 mRNA levels compared to normal controls. In contrast to the affectively ill groups, the reductions in schizophrenics were more pronounced in the left side compared to the right. Expression of poly A mRNA also showed left-sided losses in the dentate gyrus in schizophrenia but reductions in NMDAR1 remained significant when expressed as a ratio of poly A. The findings confirm a recent report of reduced hippocampal NMDAR1 mRNA in schizophrenia. However, our new evidence suggests that this is a feature of both affective and schizophrenic disorders and that schizophrenia is distinguished from the others by left-sided reductions in hippocampal NMDAR1 gene expression.
"However, there was a decrease in the CHF groups which had been subjected to stress within the hippocampus, amygdala and NAc, suggesting that the low levels of NMDAR1 may be related to a commonality between anxiety and depression. Interestingly, it was also shown that there was a reduction in NMDAR1 mRNA levels within the dentate gyrus and CA3 regions of post-mortem samples taken from schizophrenics, depressives and bipolar patients . "
"In our study, repeated MK-801 treatment decreased GluN1 mRNA expression in the hippocampus, but not in the frontal cortex and striatum, an effect that was also attenuated by CBD and clozapine. Even if contradictory results exist in the literature (Rujescu et al., 2006), reduction in mRNA expression of this subunit in the hippocampus of schizophrenia patients has been reported (Gao et al., 2000; Law and Deakin, 2001). In addition, a study using a single photon emission tomography ligand for NMDAR revealed that medication-free schizophrenia patients had lower NMDAR binding in the left hippocampus, a change not observed in clozapine-treated patients (Pilowsky et al., 2006). "
[Show abstract][Hide abstract] ABSTRACT: Background: Preclinical and clinical data suggest that cannabidiol (CBD), a major non-psychotomimetic compound from Cannabis sativa, induces antipsychotic-like effects. However, the antipsychotic properties of repeated CBD treatment have been poorly investigated. Behavioral changes induced by repeated treatment with glutamate N-methyl-D-aspartate receptor (NMDAR) antagonists have been proposed as an animal model of schizophrenia-like signs. In the present study, we evaluated if repeated treatment with CBD would attenuate the behavioral and molecular modifications induced by chronic administration of one of these antagonists, MK-801.
The International Journal of Neuropsychopharmacology 10/2014; 18(5). DOI:10.1093/ijnp/pyu041 · 4.01 Impact Factor
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