Allosteric modulation of the NMDA receptor by neurosteroids in rat brain and the impact of long term morphine administration

► Morphine subchronicly administrated rats displayed a very region and steroid specific alteration of the NMDA receptor dynamics, namely in the frontal cortex and concerning only the neurosteroid 3α5βS, not pregnenolone sulfate or DHEAS. ► The effects of the neurosteroids were mediated through allosteric modulation since no effect of morphine was recorded in the absence of the NMDA receptor antagonist ifenprodil. ► Morphine subchronicly administrated rats displayed upregulation of the NMDA receptor subunit NR2B in the frontal cortex, not in the hippocampus or the hypothalamus, which was the same region where there were changes in the 3α5βS actions due to morphine.