title: The potentiation of analgesic activity of paracetamol plus morphine involves the serotonergic system in rat brain.
abstract: OBJECTIVE
  We investigated the antinociceptive effect of subactive doses of paracetamol and morphine, given in combination.
  
  
  METHODS
  Male Wistar rats were injected with paracetamol (50 or 100 mg/kg i.p.) and morphine (2, 3 or 5 mg/kg s.c.) 10 min later and subjected to algesimetric tests 20 min thereafter.
  
  
  METHODS
  Pain threshold was evaluated in the hot-plate and formalin tests. 5-HT2 receptor binding capacity and 5-HT and 5-HIAA levels were measured in cortical and pontine areas of the brain by means of radioligand binding technique and by HPLC, respectively. Statistical analysis was done using Student-Neuman-Keul's test and 2 x 2 factorial analysis.
  
  
  RESULTS
  Only when given in combination, paracetamol (100 mg/kg) and morphine (2 and 3 mg/kg) were able to evoke an antinociceptive effect in both tests associated with an increase in 5-HT levels and a decrease in 5-HT2 receptors in the cortex. These effects were prevented by i.p. pretreatment with naloxone (1 mg/kg i.p.).
  
  
  CONCLUSIONS
  Subactive doses of paracetamol and morphine exert an analgesic effect when given in combination in the rat and indicate an involvement of both serotonergic and opiatergic systems.
authors.affiliation: Dept of Biomedical Sciences, University of Modena, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Sandrini
authors.forename: G
authors.initials: G
authors.lastname: Vitale
authors.forename: A
authors.initials: A
authors.lastname: Ottani
authors.forename: L A
authors.initials: LA
authors.lastname: Pini
mesh_terms: D000082:Acetaminophen / Q000494:pharmacology*; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004357:Drug Synergism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*
chemical_list: D018712:Analgesics, Non-Narcotic; D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D012701:Serotonin; D000082:Acetaminophen; D009270:Naloxone; D006897:Hydroxyindoleacetic Acid; D009020:Morphine