The effect of chronic haloperidol treatment on glutamate receptor subunit (GluR1, GluR2, KA1, KA2, NR1) mRNAs and glutamate binding protein mRNA in rat forebrain

Antipsychotic (neuroleptic) drugs have effects on the glutamatergic system which include changes in the expression of glutamate receptor subunits. There are, however, no long-term studies. We have investigated the influence of 16 weeks' treatment with haloperidol on eight glutamate receptor mRNAs in dorsolateral striatum, frontoparietal cortex and hippocampus using in situ hybridization histochemistry. The mRNAs targetted were the flip and flop isoforms of GluR1 and GluR2, KA1 and KA2, NR1, and the glutamate binding protein (GBP). The flip isoform of GluR2 was elevated in striatum and cortex, leading to an increase in the GluR2 flip/flop ratio. KA2 mRNA was increased in hippocampus and cortex. GBP mRNA was increased in striatum. The other mRNAs were unaffected. The data show that the profile of glutamate receptor subunit mRNA expression is altered in a molecularly and anatomically selective way following chronic haloperidol administration. They provide another indication of glutamatergic involvement in the biochemical response to antipsychotic medication.