title: Effect of rofecoxib on nociception and the serotonin system in the rat brain.
abstract: OBJECTIVE
  The purpose of the present study was to determine whether the antinociceptive activity of rofecoxib is mediated, at least in part, through changes in the brain serotonergic system.
  
  
  METHODS
  Male Wistar rats weighing 180-200 g (groups of eight) were subjected to the hot-plate and formalin tests after rofecoxib treatment. Cortical areas were removed for serotonin (5-HT) level, 5-HT2 and mu-receptor evaluation.
  
  
  METHODS
  Rofecoxib was administered orally at doses of 5, 10, 20 and 50 mg/kg for the time course evaluation in the hot-plate test (30, 60 and 120 min), and at the dose of 10 mg/kg for the formalin test and biochemical determinations.
  
  
  METHODS
  The tests performed were the hot-plate and the formalin assays. HPLC was used to determine 5-HT levels and radioligand-binding assays were utilized to evaluate the characteristics of 5-HT2 and mu-receptors. The data were analysed by ANOVA or Student's t test.
  
  
  RESULTS
  The lowest active dose of rofecoxib in the hot-plate test was 10 mg/kg. The percentage of the maximum possible effect (%MPE) values were: control = 1.7+/-3.4; treated 23.4+/-6.5 (p<0.05). The same dose had a significant effect on both phases of the formalin test. Pretreatment with p-chlorophenylalanine (PCPA) significantly decreased the activity of rofecoxib in the hot-plate test. Rofecoxib treatment increased serotonin levels and decreased the maximum number of 5-HT2 receptors. 5-HT levels (ng/g) were: control = 240.1 +/- 28.5, rofecoxib = 326.1 +/- 19.9 in the frontal cortex. The characteristics of mu-receptors did not change.
  
  
  CONCLUSIONS
  These results suggest that rofecoxib may exert its therapeutic effect, at least in part, through the central serotonergic system. The opioidergic system, on the other hand, seems to be unaffected.
authors: Department of Biomedical Science, University of Modena and Reggio Emilia, Modena, Italy. Sandrini.Maurizio@unimo.it
authors: M
authors: M
authors: Sandrini
authors: G
authors: G
authors: Vitale
authors: L A
authors: LA
authors: Pini
mesh_terms: D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007783:Lactones / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017450:Receptors, Opioid, mu / Q000032:analysis / Q000187:drug effects; D011985:Receptors, Serotonin / Q000032:analysis / Q000187:drug effects*; D012701:Serotonin / Q000032:analysis*; D013450:Sulfones
chemical_list: D018712:Analgesics, Non-Narcotic; D016861:Cyclooxygenase Inhibitors; D007783:Lactones; D017450:Receptors, Opioid, mu; D011985:Receptors, Serotonin; D013450:Sulfones; C116926:rofecoxib; D012701:Serotonin