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

• Published in: Progress in neuro-psychopharmacology & biological psychiatry 2021-12, Vol.111, p.110109-110109, Article 110109
• Main Authors: Lwin, Thit, Yang, Jenq-Lin, Ngampramuan, Sukonthar, Viwatpinyo, Kittikun, Chancharoen, Pongrung, Veschsanit, Nisarath, Pinyomahakul, Jitrapa, Govitrapong, Piyarat, Mukda, Sujira
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents - metabolism; Anti-Inflammatory Agents - pharmacology; Central Nervous System Stimulants - pharmacology; Cognitive Dysfunction - chemically induced; Cognitive impairments; Hippocampus - metabolism; Inflammation; Melatonin; Melatonin - metabolism; Melatonin - pharmacology; Methamphetamine; Methamphetamine - pharmacology; Mice; Minocycline; Myeloid Differentiation Factor 88 - metabolism; Neuroinflammation; NF-kappa B - metabolism; Signal Transduction - drug effects; Toll-like receptor 4; Toll-Like Receptor 4 - metabolism
• ISSN: 0278-5846; 1878-4216
• DOI: 10.1016/j.pnpbp.2020.110109

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. •Melatonin improves METH-induced spatial and recognition memory impairment in mice.•Melatonin attenuates METH-induced changes in the levels of proinflammatory cytokines in the serum and hippocampus.•Melatonin inhibits METH-induced astrocytosis and microgliosis in the mouse hippocampus.•Melatonin ameliorates increase of TLR4, MyD88, and pNFκB levels in the mouse hippocampus.