Opioidergic and nitrergic systems mediate the anticonvulsant effect of mefloquine and chloroquine on seizures induced by pentylenetetrazol and maximal electroshock in mice

Abstract

This study was designed to investigate the involvement of opioidergic/nitrergic systems in the anticonvulsant effect of mefloquine, compared with chloroquine, in mice. Seizures were induced by pentylenetetrazol and maximal electroshock. Mice were randomly subjected to receive mefloquine or chloroquine thirty minutes in advance. The role of opioidergic/nitrergic systems was shown by co‑administration of pharmacological intervention and nitrite levels measurement in mice hippocampi. Results indicated that mefloquine (40 mg/kg) and chloroquine (5 mg/kg) significantly decreased the occurrence of tonic hindlimb extension. Also, mefloquine 120 mg/kg and chloroquine 5 mg/kg significantly increased seizure latency and decreased mortality rate. Mefloquine decreased seizure frequency too. Besides, mefloquine (20 mg/kg) and chloroquine (5, 10 mg/kg) significantly increased seizure threshold. Interestingly, L‑NAME, 7‑NI and naltrexone pre‑treatment reversed the anticonvulsant effects of both mefloquine (20 mg/kg) and chloroquine (5 mg/kg). Moreover, co‑administration of minimal‑effective doses of morphine with mefloquine/ chloroquine (both 1 mg/kg) potentiated anticonvulsant effects, which was reversed by naltrexone and endorsed the involvement of opioid receptors. Also, nitrite levels in mice hippocampi remarkably increased after treatment with both mefloquine (20 mg/kg) and chloroquine (5 mg/kg). To conclude, mefloquine could protect the central nervous system against seizures in PTZ/MES‑induced models through opioidergic/nitrergic pathways, with similarity to chloroquine effects.