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

Background: This study evaluated the antinociceptive action of alpha-(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) 30 min prior to formalin or glutamate test and compared with a standard drug, meloxicam (10 mg/kg, ig). Results: The treatment with PSAP (10-50 mg/kg) caused inhibition in the neurogenic phase and reduced the paw oedema caused by intraplantar (ipl) injection of formalin. PSAP (1-50 mg/kg) decreased the nociceptive response in the inflammatory phase of the formalin test and in licking behaviour triggered by glutamate at doses of 0.1-50 mg/kg. The antinociceptive effect of PSAP (1 mg/kg) was abolished when the animals were pre-treated with prazosin (alpha(1)-adrenergic antagonist receptor, 0.15 mg/kg, intraperitoneally, ip), yohimbine (alpha(2)-adrenergic antagonist receptor, 1 mg/kg, ip) and sulpiride (D-2/D-3 dopamine antagonist, 5 mg/kg, ip). The antinociceptive effect of PSAP (1 mg/kg) was not abolished by WAY100635 (5-HT1A-selective serotoninergic antagonist, 0.7 mg/kg, ip), ketanserin (selective antagonist of serotonergic 5-HT2A/2C, 0.3 mg/kg, ip), ondansetron (5-HT3 selective serotoninergic antagonist, 0.5 mg/ kg, ip) or SCH23390 (D-1 dopamine receptor antagonist, 0.05 mg/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. (c) 2017 Published by Elsevier Sp. z o. o. on behalf of Institute of Pharmacology, Polish Academy of Sciences.