Regulation of immediate early gene c-fos and zif/268 mRNA expression in rat striatum by metabotropic glutamate receptor.

Metabotropic glutamate receptors are coupled to multiple intracellular second messenger systems through G-proteins and densely expressed by medium spiny projection neurons in the rat striatum. In chronically-cannulated rats, this study demonstrated that pharmacological activation of metabotropic glutamate receptors by intrastriatal injection of a selective agonist, ACPD, elevated immediate early gene c-fos and zif/268 mRNA expression in the injected dorsal striatum as revealed by quantitative in situ hybridization. The elevation of both c-fos and zif/268 was dose-dependent and the responsiveness of c-fos to ACPD at each dose surveyed was greater than that of zif/268. Induction of the two mRNAs was rapid and transient as increases in the 2 mRNAs became evident as early as 30 min, reached a peak at 1 h, and returned to normal levels 3 (c-fos) or 6 (zif/268) h, after ACPD injection. Coadministration of the selective metabotropic glutamate receptor antagonist, MCPG, with ACPD markedly attenuated ACPD-stimulated c-fos, but not zif/268, expression. Pretreatment with the ionotropic NMDA receptor antagonist, CPP, had no effect on ACPD-stimulated c-fos expression, but partially attenuated ACPD-stimulated zif/268 expression. Blockade of D1 dopamine receptors with SCH-23390 did not alter the ability of ACPD to induce the expression of these genes. These data demonstrate a difference between the profound induction of c-fos and zif/268 gene expression in response to specific activation of metabotropic glutamate receptors in striatal neurons. Furthermore, c-fos induction was independent of D1 dopaminergic and NMDA glutamatergic transmission, whereas zif/268 induction was mediated, at least in part, by NMDA receptors. Copyright 1998 Elsevier Science B.V. All rights reserved.