Opioidergic and Nitrergic Systems Mediate the Anticonvulsant Effect of Mefloquine and Chloroquine on Seizures Induced by Pentylenetetrazol and Maximal Electroshock in Mice Publisher Pubmed



Boroujeni SS^{1, 2, 3} ; Solaimanian S^{1, 2} ; Jafari RM¹ ; Sabzevari O³ ; Shafaroodi H^{1, 2} ; Maleki A^{1, 2} ; Mohammadi P^{1, 2} ; Karimi E^{1, 2} ; Dehpour AR^{1, 2} Show Affiliations
Source: Acta Neurobiologiae Experimentalis Published:2022

Abstract

This study was designed to investigate the involvement of opioidergic/nitrergic systems in the anticonvulsant effect of mefloquinecompared 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. Alsomefloquine 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 mefloquinechloroquine (both 1 mg/kg) potentiated anticonvulsant effects, which was reversed by naltrexone and endorsed the involvemenof opioid receptors. Also, nitrite levels in mice hippocampi remarkably increased after treatment with both mefloquine (20 mg/kgand 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. © 2022 by Acta Neurobiologiae Experimentalis.