mGluR5-dependent increases in immediate early gene expression in the rat striatum following acute administration of amphetamine.
Metabotropic glutamate receptor 5 (mGluR5) is densely expressed in medium-sized spiny projection neurons of the rat striatum. Activation of mGluR5 increases intracellular Ca2+, resulting in Ca(2+)-dependent cellular responses. Acute administration of the psychostimulant amphetamine (AMPH) induces immediate early gene (IEG) expression in the striatum, which is considered an important molecular event for the development of striatal neuroplasticity related to the addictive properties of drugs of abuse. This study investigated the role of mGluR5 in the mediation of IEG expression in the rat striatum induced by a single dose of AMPH (4 mg/kg, i.p.) in vivo. We found that systemic administration of the mGluR5-selective antagonist 2-methyl-6-(phenylethynyl) pyridine hydrochloride (MPEP) at a dose of 10 mg/kg, i.p. reduced AMPH-stimulated c-fos mRNA levels in the dorsal (caudoputamen) and ventral (nucleus accumbens) striatum as revealed by quantitative in situ hybridization. Similar results were observed in the three areas of cerebral cortex (cingulate, sensory, and piriform cortex). In contrast to c-fos mRNAs, AMPH-stimulated mRNA expression of another IEG, zif/268, was not significantly altered by the blockade of mGluR5 with MPEP in the entire striatum and the three areas of cortex. Treatment with MPEP alone had no effect on basal levels of c-fos and zif/268 mRNAs in the striatal and cortical areas. These results indicate that an mGluR5-dependent mechanism selectively contributes to c-fos expression in the striatum and cortex in response to acute exposure to AMPH.
Parelkar
Nikhil K
NK
Division of Pharmacy, School of Pharmacology, University of Missouri-Kansas City, 2411 Holmes Street, Room M3-225, Kansas City, MO, USA.
Wang
John Q
JQ
D000661:Amphetamine / Q000494:pharmacology*; D019969:Amphetamine-Related Disorders / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D017781:Genes, Immediate-Early / Q000187:drug effects* / Q000235:genetics; D008297:Male; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects* / Q000235:genetics
D018691:Excitatory Amino Acid Antagonists; C578937:Grm5 protein, rat; D016760:Proto-Oncogene Proteins c-fos; D011725:Pyridines; D012333:RNA, Messenger; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; C121465:6-methyl-2-(phenylethynyl)pyridine; D000661:Amphetamine