D2 dopamine receptor but not AMPA and kainate glutamate receptor genes show altered expression in response to long term treatment with trans- and cis-flupenthixol in the rat brain.
Glutamate receptor function has been hypothesized as an important factor in both the aetiology and treatment of schizophrenia. We have used a multiprobe oligonucleotide solution hybridization (MOSH) technique to examine the regulation of gene expression of the GluR1-7, KA1, and KA2 glutamate receptor subunits in the left rat brain following treatment with the optical isomers of flupenthixol at a dose of 0.2 mg kg-1 day-1 over a period of 4, 12, 24 weeks in order to understand how specific glutamate receptor genes are involved in the treatment of schizophrenia. The GluR2/3 and GluR6/7 subunit immunoreactivity in the right brain following 4 and 24 weeks of drug treatment was also examined by Western blotting. Neither trans- nor cis-flupenthixol was found to alter the gene expression of any of the 9 non-NMDA glutamate receptor subunits. On the other hand, we found a nearly two-fold increase in gene expression of the D2 dopamine receptor in specific brain regions. These results suggest that non-NMDA types of glutamate receptor subunits, in contrast to NMDA receptors, are less likely to have a role in the action of antipsychotic drugs.
D000595:Amino Acid Sequence; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D018492:Dopamine Antagonists / Q000494:pharmacology*; D005475:Flupenthixol / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D008969:Molecular Sequence Data; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000235:genetics; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D017470:Receptors, Glutamate / Q000235:genetics*; D018092:Kainic Acid Receptors / Q000235:genetics; D013237:Stereoisomerism; D013997:Time Factors