Melatonin reverts methamphetamine-induced learning and memory impairments and hippocampal alterations in mice

• Published in: Life sciences (1973) 2021-01, Vol.265, p.118844, Article 118844
• Main Authors: Veschsanit, Nisarath, Yang, Jenq-Lin, Ngampramuan, Sukonthar, Viwatpinyo, Kittikun, Pinyomahakul, Jitrapa, Lwin, Thit, Chancharoen, Pongrung, Rungruang, Saowalak, Govitrapong, Piyarat, Mukda, Sujira
• Format: Article
• Language: English
• Subjects: Animals; Brain-derived neurotrophic factor; Ca2+/calmodulin-dependent protein kinase II; Central Nervous System Stimulants - toxicity; Circadian rhythms; Cognition - drug effects; Cognitive ability; Cognitive impairment; Decision making; Density; Drug abuse; Escape learning; Functional anatomy; Glutamic acid receptors (ionotropic); Hippocampus; Hippocampus - drug effects; Hippocampus - pathology; Immunoblotting; Impairment; Latency; Learning; Male; Maze Learning - drug effects; Melatonin; Melatonin - pharmacology; Memory; Memory - drug effects; Memory Disorders - chemically induced; Memory Disorders - drug therapy; Methamphetamine; Methamphetamine - toxicity; Mice; Mice, Inbred ICR; N-Methyl-D-aspartic acid receptors; Neurons - drug effects; Neurons - pathology; Neurotoxicity; Public health; Receptors; Short term memory; Structure-function relationships; Synaptic density; Synaptophysin; TrkB receptors; Tubulin
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2020.118844

Methamphetamine (METH) has become a major public health problem because of its abuse and profound neurotoxic effects, causing alterations in brain structure and function, and impairing cognitive functions, including attention, decision making, emotional memory, and working memory. This study aimed to determine whether melatonin (MEL), the circadian-control hormone, which has roles beyond circadian rhythm regulation, could restore METH-induced cognitive and neuronal impairment. Mice were treated with either METH (1 mg/kg) or saline for 7 days, followed by MEL (10 mg/kg) or saline for another 14 days. The Morris water maze (MWM) test was performed one day after the last saline or MEL injection. The hippocampal neuronal density, synaptic density, and receptors involved in learning and memory, along with downstream signaling molecules (NMDA receptor subunits GluN2A, GluN2B, and CaMKII) were investigated by immunoblotting. METH administration significantly extended escape latency in learning phase and reduced the number of target crossings in memory test-phase as well as decreased the expression of BDNF, NMDA receptors, TrkB receptors, CaMKII, βIII tubulin, and synaptophysin. MEL treatment significantly ameliorated METH-induced increased escape latency, decreased the number of target crossings and decreased expression of BDNF, NMDA receptors, TrkB receptors, CaMKII, βIII tubulin and synaptophysin. METH administration impairs learning and memory in mice, and MEL administration restores METH-induced neuronal impairments which is probably through the changes in BDNF, NMDA receptors, TrkB receptors, CaMKII, βIII tubulin and synaptophysin. Therefore, MEL is potentially an innovative and promising treatment for learning and memory impairment of humans. •Methamphetamine (METH) administration impairs learning and memory in mice.•METH decreased the expression of synaptic molecules in the hippocampus.•Melatonin (MEL) administration restores METH-induced neuronal impairments.•MEL is a potential treatment for learning and memory impairment of humans.