Volume 28, Issue 4 (December 2024)                   Physiol Pharmacol 2024, 28(4): 430-439 | Back to browse issues page

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Rashidi S K, Ansari Dezfouli M, Khodagholi F, Dadashpour M, Shabani A A. Melatonin Attenuates Methamphetamine Neurotoxicity through inhibition of NLRP3 and pyroptosis pathway. Physiol Pharmacol 2024; 28 (4) : 6
URL: http://ppj.phypha.ir/article-1-2333-en.html
Melatonin Attenuates Methamphetamine Neurotoxicity through inhibition of NLRP3 and pyroptosis pathway
Seyed Khalil Rashidi , Mitra Ansari Dezfouli , Fariba Khodagholi , Mehdi Dadashpour , Ali Akbar Shabani
Abstract:   (766 Views)

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.

Article number: 6
Keywords: Methamphetamine, Melatonin, NLRP3, Interlukine-1β, Working memory, Pyroptosis
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Type of Manuscript: Experimental research article | Subject: Neurophysiology/Pharmacology
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