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FIGURE 2 Excitotoxicity Glutamate (Glu), which is the main excitatory neurotransmitter in the brain, has been reported to have an important role in METH-induced excitotoxicity ( 2+ influx, to trigger an increase in intracellular Ca 2+ concentration ( N -methyl-D-aspartate receptors (NMDARs) and metabotropic glutamate receptors (mGluRs) ( 2+ influx, which acts as a pervasive and pluripotent second messenger ( 2+ triggers a cascade of reactions within cells to activate protein kinases, phosphatases, and nitric oxide synthase (NOS)