title: Effect of acute and repeated administration of paracetamol on opioidergic and serotonergic systems in rats.
abstract: OBJECTIVE
  We investigated the antinociceptive effect of paracetamol or morphine after repeated administration and the changes in the characteristics of central mu-, kappa- and 5-HT2 receptors.
  
  
  METHODS
  Male rats were injected twice a day for seven days with paracetamol (400 mg/kg, i. p.) or morphine (5 mg/kg, s. c.).
  
  
  METHODS
  The antinociceptive effect was evaluated 30 min after single and multiple doses of paracetamol and morphine through the hot-plate test. Binding techniques were used to evaluate the receptor characteristics in the frontal cortex.
  
  
  RESULTS
  Both paracetamol and morphine induced an antinociceptive effect on day 1 but only paracetamol maintained this effect for seven days while morphine did not. The number of mu-opioid receptors decreased on days 1, 3, and 7 by a similar percentage after paracetamol administration (by 29, 31 and 34 %, respectively), while morphine produced a progressive decrease in comparison with controls (by 37, 49 and 60 %, respectively) and kappa-opioid receptors were unaffected. Both drugs similarly decreased the 5-HT2 receptor number on all days of treatment (by about 30 %).
  
  
  CONCLUSIONS
  The opioidergic and serotonergic systems are involved in different ways in the induction and maintenance of antinociception after paracetamol or morphine treatment.
authors.affiliation: Department of Biomedical Sciences, Sec. of Pharmacology, University of Modena and Reggio Emilia, Via G. Campi, 287-41100, Modena, Italia. Sandrini.Maurizio@unimo.it
authors.forename: M
authors.initials: M
authors.lastname: Sandrini
authors.forename: G
authors.initials: G
authors.lastname: Vitale
authors.forename: V
authors.initials: V
authors.lastname: Ruggieri
authors.forename: L A
authors.initials: LA
authors.lastname: Pini
mesh_terms: D000082:Acetaminophen / Q000494:pharmacology*; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005625:Frontal Lobe / Q000187:drug effects / Q000502:physiology; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid / Q000187:drug effects* / Q000502:physiology; D017473:Receptors, Opioid, kappa / Q000187:drug effects / Q000502:physiology; D017450:Receptors, Opioid, mu / Q000187:drug effects / Q000502:physiology; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology; D044348:Receptors, Serotonin, 5-HT2 / Q000187:drug effects / Q000502:physiology
chemical_list: D018712:Analgesics, Non-Narcotic; D009294:Narcotics; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D011985:Receptors, Serotonin; D044348:Receptors, Serotonin, 5-HT2; D000082:Acetaminophen; D009020:Morphine