title: The antinociceptive effect of trazodone in mice is mediated through both mu-opioid and serotonergic mechanisms.
abstract: The antinociceptive effects of trazodone (a triazolopyridine derivative with antidepressant activity) and its interaction with various opioid, noradrenaline and serotonin receptor subtypes were evaluated. Mice were tested with a hotplate analgesia meter. Trazodone induced a dose-dependent antinociceptive effect following i.p. administration. The ED(50) for mice in the hotplate assay for trazodone was 24.8 mg/kg (9.8; 67.4; 95% CL). The effect of opioid, adrenergic and serotonergic receptor antagonists was examined as to their ability to block trazodone antinociception. Trazodone-induced antinociception was significantly inhibited by naloxone, beta-FNA and naloxonazine, but not by nor-BNI or naltrindole, implying involvement of mu1- and mu2-opioid mechanisms. When adrenergic and serotonergic antagonists were used, metergoline (p<0.05) but not phentolamine or yohimbine, decreased antinociception elicited by trazodone, implying a clear 5-HT mechanism of antinociception. When trazodone was administered together with various agonists of the opioid receptor subtypes, it significantly potentiated antinociception mediated by mu1- and mu2- opioid receptor subtypes. Summing up these results, we conclude that the antinociceptive effect of trazodone is mainly influenced by the mu1- +mu2-opioid receptor subtype combined with the serotonergic receptor. These results explain the diffuse clinical use of trazodone in the management of some pain syndromes, and in opioid- and alcohol-detoxification programs, but raise questions regarding a possible 'indirect' opioid-dependence induced by trazodone itself.
authors.affiliation: Department of Psychiatry C, The Chaim Sheba Medical Center, 52621, Tel-HaShomer, Israel. shaulsch@netvision.net.il
authors.forename: S
authors.initials: S
authors.lastname: Schreiber
authors.forename: M M
authors.initials: MM
authors.lastname: Backer
authors.forename: I
authors.initials: I
authors.lastname: Herman
authors.forename: D
authors.initials: D
authors.lastname: Shamir
authors.forename: T
authors.initials: T
authors.lastname: Boniel
authors.forename: C G
authors.initials: CG
authors.lastname: Pick
mesh_terms: D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009292:Narcotic Antagonists / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects; D011930:Reaction Time / Q000187:drug effects; D017465:Receptors, Opioid, delta / Q000187:drug effects; D017473:Receptors, Opioid, kappa / Q000187:drug effects; D017450:Receptors, Opioid, mu / Q000187:drug effects*; D011985:Receptors, Serotonin / Q000187:drug effects*; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D014196:Trazodone / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000700:Analgesics; D009292:Narcotic Antagonists; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D011985:Receptors, Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; D014196:Trazodone