Repeated injections of dizocilpine maleate (MK-801) do not suppress the effects of nigrostriatal dopamine deafferentation on glutamate decarboxylase (GAD67) mRNA expression in the adult rat striatum

Abstract

The present study examined the effects of glutamate transmission blockade through N-methyl- d-aspartate (NMDA) receptor subtype by repeated administration of dizocilpine maleate (0.2 mg/kg, i.p., twice a day for eight days) alone or in combination with unilateral 6-hydroxydopamine-induced lesion of the nigrostriatal dopaminergic pathway on GABAergic neurons in the adult rat striatum. For this purpose, the expression of the messenger RNA encoding for the 67 kDa isoform of the GABA synthesizing enzyme, glutamate decarboxylase (GAD67 mRNA), was studied in the various conditions by quantitative in situ hybridization. The dizocilpine maleate treatment alone did not induce significant change of GAD67 mRNA levels in the striatum, indicating that NMDA receptors may not have a major role in the transcriptional regulation of GAD67 in the adult rat striatum. As reported previously, the unilateral dopaminergic lesion resulted in marked increases in GAD67 mRNA levels in the ipsilateral striatum. This up-regulation was not significantly affected by the treatment with dizocilpine maleate started 12 days after the unilateral intranigral 6-hydroxydopamine injection. Therefore, NMDA receptors are unlikely to contribute to the dopamine lesion-induced GAD67 mRNA up-regulation in striatal projection neurons. This result is of major interest in comparison with our previous finding that NMDA receptor activation is necessary to maintain the up-regulation of enkephalin expression in the striatum after dopamine lesion.