title: Comparison of the transcriptional responses induced by acute morphine, methadone and buprenorphine.
abstract: Despite their widespread use in opioid maintenance treatment and pain management, little is known about the intracellular effectors of methadone and buprenorphine and the transcriptional responses they induce. We therefore studied the acute effects of these two opioids in rats, comparing our observations with those for the reference molecule, morphine. We determined the analgesic ED50 of the three molecules in the tail flick test, to ensure that transcriptional effects were compared between doses of equivalent analgesic effect. We analysed changes in gene expression over time in three cerebral structures involved in several opioid behaviours-the dorsal striatum, thalamus and nucleus accumbens-by real-time quantitative PCR. We analysed the expression of genes encoding proteins of the endogenous opioid system in parallel with that of Fos, a marker of neuronal activation. The acute transcriptional effects of methadone resembled those of morphine more closely than did those of buprenorphine, in terms of kinetics and intensities. Our results provide the first evidence that these two drugs widely used in pain management and opioid maintenance treatment can disturb the regulation of endogenous opioid system genes and induce molecular outcomes different from those observed with morphine.
authors.affiliation: Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8206, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Belkaï
authors.forename: Dominique
authors.initials: D
authors.lastname: Crété
authors.forename: Cindie
authors.initials: C
authors.lastname: Courtin
authors.forename: Florence
authors.initials: F
authors.lastname: Noble
authors.forename: Cynthia
authors.initials: C
authors.lastname: Marie-Claire
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002047:Buprenorphine / Q000494:pharmacology; D004745:Enkephalins / Q000235:genetics; D008297:Male; D008691:Methadone / Q000494:pharmacology; D009020:Morphine / Q000494:pharmacology; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000235:genetics; D011498:Protein Precursors / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000235:genetics / Q000378:metabolism; D013788:Thalamus / Q000187:drug effects / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*; D000094942:Nociceptin Receptor
chemical_list: D000701:Analgesics, Opioid; D002047:Buprenorphine; D004745:Enkephalins; D008691:Methadone; D009020:Morphine; D011333:Pro-Opiomelanocortin; D011498:Protein Precursors; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; C033660:preproenkephalin; C000722285:Oprl1 protein, rat