Impaired preprodynorphin, but not preproenkephalin, mRNA induction in the striatum of mGluR1 mutant mice in response to acute administration of the full dopamine D(1) agonist SKF-82958.
Metabotropic glutamate receptor 1 (mGluR1) is highly expressed in striatonigral projection neurons of rat striatum. 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(1) agonist SKF-82958 was compared between mGluR1 mutant and wild-type control mice. We found that acute injection of SKF-82958 increased preprodynorphin (PPD), substance P (SP), and preproenkephalin (PPE) mRNAs in the dorsal and ventral striatum of mutant and wild-type mice in a dose-dependent 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 minus sign/minus sign mice was significantly less than that of wild-type +/+ mice in response to the two higher doses of SKF-82958. 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-type 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(1) receptor stimulation.
Mao
Limin
L
Division of Pharmacology, School of Pharmacy, University of Missouri-Kansas City, Kansas City, Missouri 64108, USA.
Conquet
François
F
Wang
John Q
JQ
D000818:Animals; D001552:Benzazepines / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004399:Dynorphins / Q000235:genetics*; D004745:Enkephalins / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D011498:Protein Precursors / Q000235:genetics*; D011699:Putamen / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D012333:RNA, Messenger / Q000032:analysis*; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D001552:Benzazepines; D004745:Enkephalins; D011498:Protein Precursors; D012333:RNA, Messenger; D017447:Receptors, Dopamine D1; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; C036448:pre-prodynorphin; D004399:Dynorphins; C071262:SK&F 82958; C033660:preproenkephalin