Pharmacological Evidence for the Possible Involvement of the Nmda Receptor Pathway in the Anticonvulsant Effect of Tramadol in Mice Publisher



Zahir M¹ ; Rashidian A^{1, 2} ; Hoseini M^{1, 2} ; Akbarian R¹ ; Chamanara M³ Show Affiliations
Source: AIMS Neuroscience Published:2022

Abstract

Background: Previous studies have shown controversial results regarding the pro or anticonvulsant effects of tramadol. Additionally, the underlying mechanism of seizure induction or alleviation by tramadol has not been fully understood. In the current study, the effects of tramadol on pentylenetetrazole (PTZ)-induced seizure and the possible involvement of the N-methyl-D-aspartate (NMDA) pathway were assessed in mice. Methods: Male Naval Medical Research Institute (NMRI) mice were treated with intravenous infusion of PTZ in order to induce clonic seizures and determine seizure threshold. Tramadol was injected intraperitoneally (0.1–150 mg/kg) 30 minutes prior to elicitation of seizures. The possible effects of intraperitoneal injections of NMDA receptor antagonists, ketamine (0.5 mg/kg) and MK-801 (0.5 mg/kg) on the anticonvulsant property of tramadol were investigated subsequently. Results: Tramadol (1–100 mg/kg) increased PTZ-induced seizure threshold in a dose-dependent, time-independent manner, with optimal anticonvulsant effect at a dose of 100 mg/kg. Acute administration of either ketamine (0.5 mg/kg) or MK-801 (0.5 mg/kg) potentiated the anticonvulsant effect of a subeffective dose of tramadol (0.3 mg/kg). Conclusion: These results suggest a possible role of the NMDA pathway in the anticonvulsant effect of tramadol. © 2022 the Author(s), licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0).