title: Effect of antagonism of the NMDA receptor on tolerance to [D-Pen2,D-Pen5]enkephalin, a delta 1-opioid receptor agonist.
abstract: The effects of MK-801, a noncompetitive antagonist of the N-methy1-D-aspartate (NMDA) receptor, and of LY 235959, a competitive antagonist of the NMDA receptor, on the development of tolerance to the analgesic action of [D-Pen2,D-Pen5]enkephalin (DPDPE), a delta 1-opioid receptor agonist were determined in mice. Tolerance to DPDPE was induced in male Swiss Webster mice by twice daily ICV injections of the drug (20 micrograms/mouse) for 4 days. To determine the effects of NMDA receptor antagonists, the drugs were injected IP in appropriate doses 10 min before each injection of DPDPE. The doses of MK-801 were 0.01, 0.03, and 0.10 mg/kg whereas those of LY 235959 were 1, 2, and 4 mg/kg. Chronic administration of NMDA receptor antagonists by themselves did not alter the tail flick response or the analgesic effect of DPDPE (10 micrograms/mouse, ICV). MK-801 given concurrently with DPDPE dose-dependently inhibited the development of tolerance to DPDPE, the significant effect being observed at 0.10 mg/kg dose. Similar inhibitory effects on the development of tolerance to DPDPE were observed with LY 235959 at 1, 2, and 4 mg/kg doses. It is concluded that antagonism of NMDA receptors blocks tolerance to the analgesic action of delta 1-opioid receptor agonist in the mouse.
authors.affiliation: Department of Pharmaceutics and Pharmacodynamics, 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: D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000008:administration & dosage / Q000494:pharmacology*; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D051379:Mice; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D017465:Receptors, Opioid, delta / Q000819:agonists*
chemical_list: D000700:Analgesics; D004745:Enkephalins; D007546:Isoquinolines; D016194:Receptors, N-Methyl-D-Aspartate; D017465:Receptors, Opioid, delta; D016291:Dizocilpine Maleate; D020881:Enkephalin, D-Penicillamine (2,5)-; C088643:LY 235959