melatonin attenuates methamphetamine neurotoxicity through inhibition of nlrp3 and pyroptosis pathway

Introduction: methamphetamine (meth) is a highly addictive psychostimulant and induces neuroinflammatory responses. melatonin is a neurohormone that has protective effects and reduces inflammation in the central nervous system. our study focused on the melatonin effect on memory impairment, nlrp3/il-1β axis, and gasdermin d and caspase-1 expression in the hippocampus of a rat model of meth use. methods: meth and melatonin were administered to the rats for 21 consecutive days. the memory was evaluated using alternation behavior in y-maze. nlrp3 and il-1β were assessed by western blotting and elisa, respectively. gasdermin d and caspase-1 expression levels were evaluated using qrt-pcr. results: the nlrp3 and il-1β were elevated in the hippocampus following meth injection. moreover, meth increased gasdermin d and caspase-1 expression levels. after 21 days of meth use, memory impairment was seen in the y-maze test. melatonin significantly improved memory and decreased the expression of nlrp3, il-1β, gasdermin d, and caspase-1 in the hippocampus. conclusion: our study revealed that inflammasome formation and pyroptosis pathway are involved in meth-induced neurotoxicity. melatonin may be a potential treatment against neurotoxicity and cognitive disorders caused by meth.