Melatonin ameliorates methamphetamine-induced cognitive impairments by inhibiting neuroinflammation via suppression of the TLR4/MyD88/NFκB signaling pathway in the mouse hippocampus.

Abstract

Methamphetamine (METH) is a highly addictive psychostimulant that causes significant health issues due to high prevalence of its illegal use. Chronic use of METH is associated with cognitive impairments in both human and animal studies, but the underlying mechanism remains unclear. METH-induced neuroinflammation is, potentially, one of the factors that causes cognitive impairments. Therefore, the present study aimed to assess whether melatonin could provide protection against inflammation, in a manner comparable to the anti-inflammatory agent, minocycline, with consequent improvements of METH-induced cognitive impairments and associated abnormalities in the mouse hippocampus. Results from the Morris water maze (MWM) test and the novel object recognition test (NORT) showed that melatonin given after METH injections could ameliorate both METH-induced spatial and recognition memory impairments. These memory impairments are associated with changes in the neuroinflammatory profiles, including IL-6, IL-1β, and TNF-α, both in the blood serum and hippocampus of adult mice. METH-treated mice also exhibited reactive astrocytes and activated microglia in the hippocampus. METH-induced activation of glial cells is associated with the activation of the TLR4/MyD88/NFκB signaling pathway. Moreover, melatonin administration led to recovery of these METH-induced markers to control levels. Thus, we conclude that melatonin could potentially be used as a cognitive enhancer and anti-inflammatory agent in the treatment of METH use disorder in humans.

• Authors: Thit Lwin, Jenq-Lin Yang, Sukonthar Ngampramuan, Kittikun Viwatpinyo, Pongrung Chancharoen, Nisarath Veschsanit, Jitrapa Pinyomahakul, Piyarat Govitrapong, Sujira Mukda
• Journal: Progress in neuro-psychopharmacology & biological psychiatry (Prog Neuropsychopharmacol Biol Psychiatry) Vol. 111 Pg. 110109 (12 20 2021) ISSN: 1878-4216 [Electronic] England
• PMID: 32941923 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Elsevier Inc. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Central Nervous System Stimulants
• Myeloid Differentiation Factor 88
• NF-kappa B
• Toll-Like Receptor 4
• Methamphetamine
• Melatonin

Topics

• Animals
• Anti-Inflammatory Agents (metabolism, pharmacology)
• Central Nervous System Stimulants (pharmacology)
• Cognitive Dysfunction (chemically induced)
• Hippocampus (metabolism)
• Inflammation
• Melatonin (metabolism, pharmacology)
• Methamphetamine (pharmacology)
• Mice
• Myeloid Differentiation Factor 88 (metabolism)
• NF-kappa B (metabolism)
• Signal Transduction (drug effects)
• Toll-Like Receptor 4 (metabolism)