title: Different effects of L-arginine on morphine tolerance in sham and ovariectomized female mice.
abstract: OBJECTIVE
  The roles of gonadal hormones and nitric oxide (NO) on the analgesic effects of morphine, tolerance to morphine, and their interactions have been widely investigated. In the present study, the effect of L-arginine (an NO precursor) on morphine tolerance in sham and ovariectomized (OVX) female mice was investigated.
  
  
  METHODS
  Forty mice were divided into sham and OVX groups. On the first day, a hot plate test ((55±0.2) °C; cut-off 30 s) was carried out as a base record 15 min before injection of morphine (10 mg/kg, subcutaneously (s.c.)) and was repeated every 15 min after injection. The sham group was then divided into two subgroups: sham-tolerance-L-arginine (Sham-Tol-LA) and sham-tolerance-saline (Sham-Tol-Sal) which received either L-arginine 50 mg/kg (intraperitoneally (i.p.)) or saline 10 ml/kg (i.p.), respectively, three times in a day for three consecutive days. Morphine tolerance was induced in animals by injecting 30 mg/kg morphine (s.c.) three times/day for three days. This treatment was also used for OVX subgroups. On the fifth day, the hot plate test was repeated. The analgesic effect of morphine was calculated as the maximal percent effect (MPE). The results were compared using repeated measure analysis of variance (ANOVA).
  
  
  RESULTS
  There was no significant difference in MPE between the OVX and sham groups. The MPEs in both the Sham-Tol-Sal and OVX-Tol-Sal groups were lower than those in both the sham and OVX groups (P<0.01). The MPE in the OVX-Tol-Sal group was greater than that in the Sham-Tol-Sal group (P<0.01). The MPE in the Sham-Tol-LA group was higher than that in the Sham-Tol-Sal group (P<0.01). However, there was no significant difference between the Sham-Tol-LA and sham groups or between the OVX-Tol-LA and OVX-Tol-Sal groups.
  
  
  CONCLUSIONS
  The results of the present study showed that repeated administration of morphine causes tolerance to the analgesic effect of morphine. L-arginine could prevent tolerance to morphine but its effect was different in the presence of ovarian hormones.
authors.affiliation: Neuroscience Research Center and Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Iran.
authors.forename: Reza
authors.initials: R
authors.lastname: Karami
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Hosseini
authors.forename: Fatimeh
authors.initials: F
authors.lastname: Khodabandehloo
authors.forename: Leila
authors.initials: L
authors.lastname: Khatami
authors.forename: Zahra
authors.initials: Z
authors.lastname: Taiarani
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage; D000818:Animals; D001120:Arginine / Q000008:administration & dosage*; D004347:Drug Interactions; D004361:Drug Tolerance; D005260:Female; D042341:Gonadal Hormones / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009020:Morphine / Q000008:administration & dosage*; D009569:Nitric Oxide / Q000378:metabolism*; D010052:Ovariectomy; D010146:Pain / Q000188:drug therapy* / Q000503:physiopathology*
chemical_list: D000701:Analgesics, Opioid; D042341:Gonadal Hormones; D009569:Nitric Oxide; D009020:Morphine; D001120:Arginine