Regulation of ionotropic glutamate receptor subunits in different rat brain areas by a preferential sigma1 receptor ligand and potential atypical antipsychotic

The effect of chronic administration of the putative atypical antipsychotic E-5842, a preferential sigma(1) receptor ligand, on ionotropic glutamate receptor subunit levels of mRNA and protein, was studies. The repeated administration of E-5842 differentially regulated levels of the NMDA-2A and of GluR2 subunits in a regionally specific way. Levels of immunoreactivity for the NMDA-2A subunit were upregulated in the medical prefrontal cortex, the frontoparietal cortex, the cingulate cortex, and in the dorsal striatum, while they were down-regulated in the nucleus accumbens. Levels of the GluR2 subunit of the AMPA receptors were up-regulated in the medial prefrontal cortex and the nucleus accumbens and down-regulation was observed in the dorso-lateral striatum. Regulation of the levels of mRNA for the different subunits was also observed in some cases. The results show that E-5842, through a mechanisms still unknown, is able to modify levels of several glutamate receptor subunits and these changes could be related to its antipsychotic activity in preclinical tests. (C) American College of Neuropsychopharmacology. Published by Elsevier Science Inc.