title: Suppression of naloxone-precipitated withdrawal jumps in morphine-dependent mice by stimulation of prostaglandin EP3 receptor.
abstract: 1. We have shown that intracisternal (i.c.) administration of interleukin-1 beta (IL-1 beta) attenuates naloxone-precipitated withdrawal jumps in morphine-dependent mice, and the effect was partly mediated by the corticotropin-releasing factor. To elucidate further other possible mechanisms involved in the inhibitory effect of IL-1 beta on morphine withdrawal jumping behaviour, in this study, we examined the involvement of the prostaglandin-synthesis pathway, because prostaglandins have been shown to mediate the several central effects of IL-1. Furthermore, we examined the effects of subtype-selective prostaglandin receptor agonists on morphine withdrawal jumping behaviour. 2. Mice were rendered morphine-dependent by subcutaneous implantation of a pellet containing 11.5 +/- 0.3 mg morphine hydrochloride for 48 h. Morphine withdrawal syndromes were precipitated by intraperitoneal (i.p.) injection of naloxone (10 mg kg-1). The degree of physical dependence on morphine was estimated by counting the number of jumps, one of the typical withdrawal signs in mice, for 40 min. 3. The inhibitory effect of IL-1 beta (1 ng/mouse) administered intracisternally 30 min before naloxone (10 mg kg-1, i.p.) was significantly blocked by pretreatment with sodium salicylate (a cyclo-oxygenase inhibitor, 10 ng or 30 ng/mouse) administered intracisternally 15 min before IL-1 beta, while i.c. administration of sodium salicylate alone (3 ng, 10 ng or 30 ng/mouse) followed by i.c. administration of vehicle instead of IL-1 beta did not significantly change the number of jumps precipitated by naloxone. 4. Intracisternal administration of M&B28,767 (an EP3-receptor agonist, 1 fg-30 ng/mouse) and sulprostone (an EP1/EP3-receptor agonist, 10 fg-100 ng/mouse) 30 min before naloxone (10 mg kg,-1 i.p.) attenuated withdrawal jumps with a U-shaped dose-response, reaching a peak at 10 pg/mouse and 100 pg/mouse, respectively. On the other hand, i.c. administration of iloprost (an EP1/IP-receptor agonist, 10 fg-100 ng/mouse), butaprost (an EP2-receptor agonist, 10 fg-100 ng/mouse) or prostaglandin F2 alpha (a FP-receptor agonist, 10 fg-100 ng/mouse) 30 min before naloxone (10 mg kg-1, i.p.) did not significantly change the number of jumps precipitated by naloxone. 5. These results indicate that the prostaglandin-synthesis pathway is, at least in part, involved in the inhibitory effect of IL-1 beta on naloxone-precipitated withdrawal jumps in morphine-dependent mice, and that the prostaglandin synthesized in the brain suppresses the morphine withdrawal jumping behaviour via the EP3-receptor, but not via the EP1-, EP2-, IP- or FP-receptor.
authors.affiliation: Department of Molecular Pharmacology, Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Nakagawa
authors.forename: M
authors.initials: M
authors.lastname: Minami
authors.forename: S
authors.initials: S
authors.lastname: Katsumata
authors.forename: Y
authors.initials: Y
authors.lastname: Ienaga
authors.forename: M
authors.initials: M
authors.lastname: Satoh
mesh_terms: D000527:Alprostadil / Q000031:analogs & derivatives / Q000494:pharmacology; D000701:Analgesics, Opioid; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D015237:Dinoprost / Q000494:pharmacology; D015232:Dinoprostone / Q000031:analogs & derivatives / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009020:Morphine; D009270:Naloxone / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology*; D011453:Prostaglandins / Q000378:metabolism; D018078:Receptors, Prostaglandin E / Q000819:agonists* / Q000502:physiology; D012980:Sodium Salicylate / Q000494:pharmacology; D013268:Stimulation, Chemical; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy* / Q000378:metabolism; D019966:Substance-Related Disorders / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D000701:Analgesics, Opioid; D007375:Interleukin-1; D011453:Prostaglandins; D018078:Receptors, Prostaglandin E; D009270:Naloxone; C016767:sulprostone; D009020:Morphine; D015237:Dinoprost; D000527:Alprostadil; C048491:butaprost; D015232:Dinoprostone; D012980:Sodium Salicylate