Selective activation of group I metabotropic glutamate receptors upregulates preprodynorphin, substance P, and preproenkephalin mRNA expression in rat dorsal striatum

Group I metabotropic glutamate receptors (mGluRs) are positively coupled to phosphoinositide hydrolysis through G-proteins and are densely expressed i n the medium-sized spiny neurons of striatum. Activation of this group of m GluRs in the striatum produces long-lasting stimulation of behavioral activ ity. In this study, the role of group I mGluRs in the modulation of neurope ptide mRNA expression in striatal neurons was investigated using a Group I- selective agonist, 3,5-dihydroxyphenylglycine (DHPG) in chronically cannula ted rats. Unilateral injections of DHPG into the dorsal striatum (caudoputa men) at behaviorally active doses of 20, 40, and 80 nmol elevated basal lev els of preprodynorphin (PPD), substance P (SP), and preproenkephalin (PPE) mRNAs in the injected dorsal striatum as revealed by quantitative in situ h ybridization. The elevation of all three mRNAs was dose-dependent and the r esponsiveness of opioid peptide mRNAs (PPD and PPE) to acute injection of D HPG at each dose surveyed was greater than that of SP mRNA. Induction of th e mRNAs was delayed and prolonged as increases in hybridization signal beca me evident at 2 (SP and PPE) or 3 (PPD) h, reached a peak between 3 and 6 h , and returned to normal levels 24 h after DHPG injection. Coadministration of a Group I-selective antagonist, n-phenyl-7-(hydroxyimino)cyclopropa[b]c hromen-1a-carboxamide (PHCCC, 10 nmol), with DHPG markedly attenuated DHPG- stimulated PPD, PPE, and, to a lesser extent, SP expression. Administration of PHCCC alone had no significant effect on basal levels of three mRNA exp ression in the striatum. This study provides a detailed description of the dose- and time-related alterations in striatonigral PPD/SP and striatopalli dal PPE mRNA expression in response to a single injection of the Group I ag onist DHPG. Data obtained demonstrate a facilitatory, dynamic regulation of constitutive expression of PPD, SP, and PPE mRNAs by local enhancement of glutamatergic tone on DHPG- and PHCCC-sensitive Group I mGluRs. (C) 2001 Wi ley-Liss, Inc.