Contribution of dopaminergic and noradrenergic systems in the antinociceptive effect of α-(phenylalanyl) acetophenone

Abstract

Background: This study evaluated the antinociceptive action of α-(phenylalanyl) acetophenone (PSAP) in mice.

Methods: Evaluated whether the serotonergic, adrenergic and dopaminergic systems are involved in PSAP antinociceptive activity. PSAP was administered intragastrically (ig) 30min prior to formalin or glutamate test and compared with a standard drug, meloxicam (10mg/kg, ig).

Results: The treatment with PSAP (10-50mg/kg) caused inhibition in the neurogenic phase and reduced the paw oedema caused by intraplantar (ipl) injection of formalin. PSAP (1-50mg/kg) decreased the nociceptive response in the inflammatory phase of the formalin test and in licking behaviour triggered by glutamate at doses of 0.1-50mg/kg. The antinociceptive effect of PSAP (1mg/kg) was abolished when the animals were pre-treated with prazosin (α₁-adrenergic antagonist receptor, 0.15mg/kg, intraperitoneally, ip), yohimbine (α₂-adrenergic antagonist receptor, 1mg/kg, ip) and sulpiride (D₂/D₃ dopamine antagonist, 5mg/kg, ip). The antinociceptive effect of PSAP (1mg/kg) was not abolished by WAY100635 (5-HT_1A-selective serotoninergic antagonist, 0.7mg/kg, ip), ketanserin (selective antagonist of serotonergic 5-HT_2A/2C, 0.3mg/kg, ip), ondansetron (5-HT₃ selective serotoninergic antagonist, 0.5mg/kg, ip) or SCH23390 (D₁ dopamine receptor antagonist, 0.05mg/kg, ip) in the glutamate test. No changes in locomotor activity were observed in the animals treated with PSAP and/or antagonists in the open field test.

Conclusion: These results showed the antinociceptive action of PSAP in formalin and glutamate tests and the involvement of the dopaminergic and adrenergic systems in its antinociceptive activity.

Keywords: Formalin; Glutamate; Nociception; Organoselenium; Selenium.