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The present experiment was designed to test the effects of direct activation of the NMDA or AMPA types of GLU receptor on the levels of two mRNAs that encode the peptide cotransmitters met<jats:sup>5<\/jats:sup>\u2010enkephalin (ME) and sub\u2010 stance P (SP). In situ hybridization histochemistry of forebrain tissue sections from rats 8 h after a single intracerebroventricular infusion of NMDA or AMPA revealed a significant and dose\u2010dependent elevation (to a maximum of almost 50%) of striatal ME mRNA when compared to vehicle\u2010injected controls. SP mRNA was not significantly affected. NMDA was more effective than AMPA over the dose range used. Pretreatment with a potent and highly specific AMPA antagonist (NBQX) predictably blocked the AMPA\u2010mediated elevation, and was only slightly effective against the NMDA\u2010induced response. In striking contrast, pretreatment with a potent and highly selective NMDA antagonist (CGP37849) fully opposed both the NMDA\u2010 and the AMPA\u2010mediated elevation of ME mRNA. These data further implicate the NMDA receptor in the regulation of peptide cotransmitter gene transcription. They suggest also that the AMPA receptor may play an indirect, synergistic role in the genetic responses of striatal neurons to GLU transmission. \u00a9 1995 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/syn.890210409","type":"journal-article","created":{"date-parts":[[2004,12,31]],"date-time":"2004-12-31T22:26:45Z","timestamp":1104532005000},"page":"342-347","source":"Crossref","is-referenced-by-count":20,"title":["N\u2010methyl\u2010D\u2010aspartate acutely increases proenkephalin mRNA in the rat striatum"],"prefix":"10.1002","volume":"21","author":[{"given":"R. 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