Regulation of ionotropic glutamate receptor subunits in different rat brain areas by a preferential sigma(1) 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 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.
Guitart
X
X
Department of Neuropharmacology, Research Center, Laboratoris Esteve, S.A., Barcelona, Spain. xguitart@esteve.es
Méndez
R
R
Ovalle
S
S
Andreu
F
F
Carceller
A
A
Farré
A J
AJ
Zamanillo
D
D
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D015152:Blotting, Northern; D015153:Blotting, Western; D001923:Brain Chemistry / Q000187:drug effects*; D008024:Ligands; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology*; D015347:RNA Probes; D012333:RNA, Messenger / Q000096:biosynthesis / Q000302:isolation & purification; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000187:drug effects; D017470:Receptors, Glutamate / Q000187:drug effects*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D017480:Receptors, sigma / Q000187:drug effects*; D014230:Triazoles / Q000494:pharmacology*
D014150:Antipsychotic Agents; C117757:E 5842; D008024:Ligands; D009419:Nerve Tissue Proteins; D011725:Pyridines; D015347:RNA Probes; D012333:RNA, Messenger; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D017480:Receptors, sigma; D014230:Triazoles