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To define the role of mGluR1 in the regulation of striatal gene expression, the responsiveness of the three neuropeptide gene expression to a single injection of the dopamine D<jats:sub>1<\/jats:sub> agonist SKF\u201082958 was compared between mGluR1 mutant and wild\u2010type control mice. We found that acute injection of SKF\u201082958 increased preprodynorphin (PPD), substance P (SP), and preproenkephalin (PPE) mRNAs in the dorsal and ventral striatum of mutant and wild\u2010type mice in a dose\u2010dependent manner (0.125, 0.5, and 2 mg\/kg, i.p.) as revealed by quantitative in situ hybridization. However, the induction of PPD mRNA in both the dorsal and ventral striatum of mGluR1 \u2212\/\u2212 mice was significantly less than that of wild\u2010type +\/+ mice in response to the two higher doses of SKF\u201082958. In contrast to PPD, SP and PPE in the dorsal and ventral striatum of mGluR1 mutant mice were elevated to a similar level as that of wild\u2010type mice. There were no differences in basal levels and distribution patterns of all three mRNAs between the two genotypes of mice treated with saline. These results indicate that mGluR1 selectively participates in striatonigral PPD induction in response to D<jats:sub>1<\/jats:sub> receptor stimulation. 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