EXPRESSION OF MESSENGER-RNAS ENCODING IONOTROPIC GLUTAMATE RECEPTORS IN RAT-BRAIN - REGULATION BY HALOPERIDOL

In situ hybridization was used to study the regional distribution of m essenger RNAs encoding ionotropic glutamate receptor subtypes in the r at brain's dopaminergic cell body regions and their forebrain projecti on areas. Short oligonucleotide probes specific for the messenger RNAs encoding the flip or flop splice forms of the GluR1 and GluR2 AMPA ha -amino-3-hydroxy-5-methyl-4-isoxazolepropionate) receptor subunits, or for the messenger RNAs encoding the N-methyl-D-aspartate R1 subunit, were used. Significant differences were seen in the relative messenger RNA levels, and the distribution of the flip and flop splice forms, o f GluR1 and GluR2. In the dopaminergic cell groups of the substantia n igra pars compacta and the ventral tegmental area, the flip form of bo th GluR1 and GluR2 dominated over the flop form. Similarly, in the cor e division of the nucleus accumbens, GluR1 and GluR2 flip forms domina ted over the flop forms. In contrast, in the accumbens shell, the GluR 1 and GluR2 hop forms dominated over the flip forms. As a comparison t o the AMPA receptor subunits, N-methyl-D-aspartate RI messenger RNA wa s relatively evenly distributed in all the regions analysed. The resul ts demonstrate a heterogeneous distribution of the flip and flop splic e forms of GluR1 and GluR2 in the brain's dopaminergic pathways, which could contribute to physiological differences in regulation of the pa thways by glutamatergic neurotransmission. We also studied regulation of glutamate receptor subunit expression in these regions by antipsych otic drugs, based on previous reports of altered levels of subunit imm unoreactivity after drug treatment. Chronic administration of the typi cal antipsychotic drug, haloperidol, caused a small but significant in duction of GluR2 flip messenger RNA in the dorsolateral caudate-putame n. This effect was not seen after chronic administration of the atypic al antipsychotic drug, clozapine. Significant drug regulation of the o ther glutamate receptor subunits studied was not observed. (C) 1998 IB RO. Published by Elsevier Science Ltd.