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[20] Physical dependence on opioids has become observed to make an elevation of extracellular glutamate, an increase in NMDA receptor subunits NR1 and NR2A, phosphorylated CaMKII, and c-fos. Expression of CaMKII and c-fos is attenuated by NMDA receptor antagonists, which can be connected to blunted withdrawal in adult rats, but not neonatal rats[21