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Effects of phencyclidine on excitatory amino acid activation of spinal interneurones in the cat

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    Accurate calibration of excitatory–inhibitory balance across the central nervous system is fundamental for the normal functioning of the brain, while an imbalance in neuronal excitation/inhibition is a core feature observed in neuropsychiatric disorders, but not restricted to schizophrenia. The finding [37] that the psychotomimetic drug phencyclidine noncompetitively blocked the N-methyl-d-aspartate receptor (NMDAR) gave rise to the glutamate theory of schizophrenia [10, 11, 26], according to which NMDAR hypofunction and disturbances in NMDAR-related gene expression and metabolic pathways confer the disease phenotypes [46, 62]. The NMDAR antagonist ketamine has been shown to induce significant psychosis [31] and exacerbated it further in individuals predisposed to schizophrenia symptomatology [32].

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