Chronic morphine treatment alters expression of N-methyl-D-aspartate receptor subunits in the extended amygdala.

The nucleus accumbens (NAcc) and central amygdala (CeA) are parts of the extended amygdala, a complex that plays a key role in drug abuse and dependence. Our previous studies showed that opiates and ethanol alter glutamatergic transmission in these regions. N-methyl-D-aspartate (NMDA) receptors are key components of glutamatergic transmission likely involved in the development of opiate tolerance and dependence. In this study we examined the effects of chronic morphine administration on gene and protein expression of three major NMDA receptors subunits (NR1, NR2A, and NR2B) in NAcc and CeA. Real-time PCR showed no differences in mRNA levels of any of the subunits in the whole NAcc between naïve and morphine-dependent rats. However, at the protein level, immunoblotting revealed that chronic morphine significantly increased levels of NR1 and NR2B subunits. In contrast to the case for NAcc, in CeA we found an increased mRNA level for the NR1 subunit only but unchanged protein levels of all three subunits in morphine-dependent rats. The altered expressions of NMDA receptor subunits, especially in NAcc, of morphine-dependent rats may represent a neuroadaptation to chronic morphine and suggest a mechanism for the changes of glutamatergic transmission found in the extended amygdala in dependent rats. In addition, our results indicate a region-specific response of NMDA receptor subunits to chronic morphine administration at the gene and protein levels. Copyright 2006 Wiley-Liss, Inc.