Heroin exposure and withdrawal differentially influence expression of NMDA receptor NR2 subunits in the prelimbic region of rat medial prefrontal cortex

Abstract It is widely reported that drug addiction involves the strengthening of specific reward circuits through N-methyl-D-aspartic acid receptor (NMDAR)-dependent synaptic potentiation, and several lines of evidence strongly implicate NMDA receptor 2 (NR2) subunits in drug abuse. To explore the potential mechanism of heroin dependence, this study examined changes in the expression levels of NR2 subunits NR2A–D in the prelimbic (PL) region of the medial prefrontal cortex (mPFC) after repeated heroin administration and subsequent abstinence. The conditioned place preference (CPP) test confirmed successful induction of heroin dependence and withdrawal. Western blotting and qRT-PCR revealed no differences in NR2A subunit expression among heroin-exposure, heroin-withdrawal, and control group rats; in contrast, expression of NR2B was significantly higher in the heroin-exposure group, whereas expression levels of NR2C and NR2D were significantly higher in the heroin-withdrawal group relative to the controls. Further studies are needed to identify the functional significance based on alterations of NR2 subunits.