Analgesic effect of supraphysiological doses of melatonin in mice is not relayed by aryl hydrocarbon receptors (AhR)

Aim/objective When applied in pharmacological doses, the indole derivative melatonin is neuroactive and neuroprotective. Indoles and their metabolites, such as kynurenine, are ligands of aryl hydrocarbon receptors (AhR). This study aimed to evaluate the analgesic activity of melatonin. The possible involvement of AhR and kynurenine in its neuropharmacological effects were also tested. Methods . After intraperitoneal injection of melatonin (30, 100, or 300 mg/kg) for seven days with or without alpha naphthoflavone (ANF) pretreatment, male mice ICR (25‐30 g) were evaluated. Two tests for analgesia, i.e., the hot plate test and the formalin test, were applied. AhR and kynurenine concentrations were measured in brain homogenates. Results . Dose‐dependent analgesic activity of the melatonin in parallel with the increase of AhR and kynurenine levels was observed. However, the antagonist ANF neither possess analgesic activity itself, nor blocks the analgesic effect of the melatonin, despite increasing both AhR and kynurenine dose‐dependently. Conclusion . Our results do not support the involvement of AhR in the demonstrated neurobiological activity. Further studies are needed to elucidate their exact molecular mechanisms.