title: Nitric oxide synthase inhibition attenuates tolerance to morphine but not to [D-Ala2, Glu4] deltorphin II, a delta 2-opioid receptor agonist in mice.
abstract: The effects of NG-nitro-L-arginine (L-NNA) and NG-monomethyl-L-arginine (L-NMMA), two potent inhibitors of nitric oxide synthase (NOS) on the development of tolerance to the analgesic action of [D-Ala2, Glu4] deltorphin II (deltorphin II), a delta 2-opioid receptor agonist, and morphine, a mu-opioid receptor agonist, were determined in mice. Male Swiss-Webster mice were rendered tolerant to deltorphin II by twice daily ICV injections of the drug for 4 days. Tolerance to morphine was induced by twice daily s.c. injections of the drug for 4 days. Multiple injections of deltorphin II (20 micrograms/mouse) or morphine (15 mg/kg) resulted in the development of tolerance to their analgesic action as evidenced by decreases in the response in comparison to mice injected with vehicle. Concurrent administration of L-NNA or L-NMMA (2,4, or 8 mg/kg, i.p.) had no effect on the development of tolerance to the analgesic action of deltorphin II. However, the same doses of L-NNA or L-NMMA inhibited the development of tolerance to the analgesic action of morphine. Acute treatment with L-NNA or L-NMMA did not modify deltorphin II- or morphine-induced analgesia in mice. It is concluded that NOS inhibition attenuates tolerance to the analgesic action of morphine but not to that of deltorphin II, a delta 2-opioid receptor agonist, in the mouse.
authors.affiliation: Department of Pharmaceutics and Pharmacodynamics (M/C 865), University of Illinois at Chicago, 60612, USA.
authors.forename: G M
authors.initials: GM
authors.lastname: Zhao
authors.forename: H N
authors.initials: HN
authors.lastname: Bhargava
mesh_terms: D000698:Analgesia; D000818:Animals; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology; D004361:Drug Tolerance; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D019335:Nitroarginine / Q000008:administration & dosage / Q000494:pharmacology*; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology*; D017465:Receptors, Opioid, delta / Q000819:agonists*; D019323:omega-N-Methylarginine / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D009842:Oligopeptides; D017465:Receptors, Opioid, delta; C060209:deltorphin II, Ala(2)-; D019335:Nitroarginine; D019323:omega-N-Methylarginine; D009020:Morphine; D019001:Nitric Oxide Synthase