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Other changes brought on by repeated cocaine exposure include: an upregulation of NMDA receptor binding in the regions such as the cortex, striatum, amygdala and hippocampus has been reported following repeated cocaine exposure [124-126] but see [127] a decrease in NR1 and/or NR2B/2C expression in regions such as globus pallidus, subiculum, striatum, and cerebellum [98, 105] an up-regulation of NR1 and a down-regulation of GluR2-7 and KA2 expression in cerebral cortex [97, 108, 128] increased phosphorylation of GluR1 in the prefrontal cortex [115] an increase in mGluR5 expression in the hippocampus [129] bidirectional alterations in the expression of NMDA and AMPA receptor subunit expression in the amygdala [130, 131] A role for glutamatergic transmission in the rewarding and reinforcing effects of cocaine has been clearly demonstrated by pharmacological studies utilizing iGluR antagonists

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