title: NO synthase inhibitors reduce opioid desensitization in rat locus coeruleus neurons in vitro.
abstract: The aim of this study was to examine by electrophysiological techniques whether nitric oxide (NO) is involved in the development of desensitization to the opioid agonist Met5-enkephalin (ME) in locus coeruleus neurons from rat brain slices. Bath perfusion with ME (0.05-1.6 microM) caused a concentration-dependent reduction in the firing rate of locus coeruleus cells, whereas perfusion with a high concentration of ME (10 microM) desensitized the inhibitory effect of subsequent ME (0.8 microM) applications. However, in slices perfused with the NO synthase inhibitors 7-NI (100 microM), L-NAME (100 microM) or L-NA (100 microM) the ME (10 microM)-induced opioid desensitization was strongly attenuated. The effect of L-NAME was prevented by administration of L-arginine (100 microM). These results suggest that nitric oxide may contribute to opioid desensitization in locus coeruleus neurons.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of the Basque Country (UPV/EHU), Leioa, Bizkaia, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Torrecilla
authors.forename: J
authors.initials: J
authors.lastname: Pineda
authors.forename: L
authors.initials: L
authors.lastname: Ugedo
mesh_terms: D000818:Animals; D004594:Electrophysiology; D004744:Enkephalin, Methionine / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D066298:In Vitro Techniques; D007191:Indazoles / Q000494:pharmacology; D008125:Locus Coeruleus / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D019335:Nitroarginine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000187:drug effects*
chemical_list: D004791:Enzyme Inhibitors; D007191:Indazoles; D017450:Receptors, Opioid, mu; D019335:Nitroarginine; D004744:Enkephalin, Methionine; D019001:Nitric Oxide Synthase; C080122:7-nitroindazole; D019331:NG-Nitroarginine Methyl Ester