title: Opioid system mediated anti-nociceptive effect of agomelatine in mice.
abstract: OBJECTIVE
  This study was planned to examine the antinociceptive efficacy of agomelatine against acute mechanical, thermal, and chemical nociceptive stimuli, as well as to determine the opioid receptor subtypes mediating these effects.
  
  
  METHODS
  Tail-clip, hot-plate, and acetic acid-induced writhing tests were performed to evaluate anti-nociceptive effect. Besides, possible effect of agomelatine on the motor coordination of animals was assessed with a Rota-rod test.
  
  
  RESULTS
  Agomelatine (40mg/kg and 60mg/kg) significantly prolonged the reaction time of mice in both the tail-clip and hot-plate tests, suggesting the antinociceptive activity is related to both spinal and supraspinal mechanisms. This drug also reduced the number of writhing behaviors indicating the presence of a peripherally mediated antinociceptive effect. Rota-rod testing displayed no notable effect on the motor activity of the animal supporting the conclusion that the observed antinociceptive effect is specific. The agomelatine-induced antinociceptive activity abrogated following pretreatment with naloxone (a non-selective opioid receptor antagonist, 5.48mg/kg, i.p.), which suggested the participation of opioid mechanisms to the antinociception. The possible contribution of μ, δ and ҡ subtypes of opioid receptors to the anti-nociceptive effect were evaluated using naloxonazine (7mg/kg, s.c.), naltrindole (0.99mg/kg, i.p.), and nor-binaltorphimine (1.03mg/kg, i.p.), respectively. Pretreatments using these antagonists abolished the antinociceptive activity of agomelatine in all of the nociceptive test paradigms used, which pointed out that μ, δ, and ҡ opioid receptors participated to the action of agomelatine on pain.
  
  
  CONCLUSIONS
  These results demonstrated the therapeutic potential of agomelatine in the treatment of pain disorders.
authors: Anadolu University Graduate School of Health Sciences, Department of Pharmacology, 26470 Eskişehir, Turkey.
authors: Merve
authors: M
authors: Kasap
authors: Anadolu University, Faculty of Pharmacy, Department of Pharmacology, 26470 Eskişehir, Turkey. Electronic address: ozgurdt@anadolu.edu.tr.
authors: Özgür Devrim
authors: ÖD
authors: Can
mesh_terms: D000081:Acetamides / Q000494:pharmacology*; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009270:Naloxone / Q000031:analogs & derivatives / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy* / Q000517:prevention & control*; D010147:Pain Measurement / Q000187:drug effects*; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors*; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors*; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors*; D045442:Rotarod Performance Test; D009281:Naphthalenes
chemical_list: D000081:Acetamides; D000700:Analgesics; D009270:Naloxone; D009271:Naltrexone; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; C084711:agomelatine; D009281:Naphthalenes; C051844:norbinaltorphimine; C034643:naloxonazine; C055382:naltrindole
keywords: Acetic acid-induced writhing test; Agomelatine; Hot-plate test; Opioid receptor; Tail-clip test