The antinociceptive effect of trazodone in mice is mediated through both μ-opioid and serotonergic mechanisms

Shaul Schreiber*, Maria M. Backer, Isachar Herman, David Shamir, Tal Boniel, Chaim G. Pick

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

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 ED50 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, β-FNA and naloxonazine, but not by nor-BNI or naltrindole, implying involvement of μ1- and μ2-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 μ1- and μ2-opioid receptor subtypes. Summing up these results, we conclude that the antinociceptive effect of trazodone is mainly influenced by the μ1- + μ2-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. (C) 2000 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)51-56
Number of pages6
JournalBehavioural Brain Research
Volume114
Issue number1-2
DOIs
StatePublished - 1 Sep 2000

Keywords

  • Antidepressants
  • Antinociception
  • Hotplate
  • Opioid receptor subtypes
  • Pain
  • Serotonin
  • Trazodone

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