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 studied. 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 up-regulated in the medial 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 receptor 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 mechanism still unknown, is able to modify levels of several glutamate receptor subunits and these changes could be related to its antipsychotic activity in pre-clinical tests.
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