Expression and colocalization of NMDA receptor and FosB/ΔFosB in sensitive brain regions in rats after chronic morphine exposure

Research in the last decade demonstrated that the NMDA receptor (NMDAR) has an important role in opiate-induced neural and behavioral plasticity. In addition, increased levels of FosB-like proteins (FosB/Delta FosB) were found to be related to morphine withdrawal behaviors. However, the relationship between NMDAR and FosB/Delta FosB in sensitive brain regions during morphine withdrawal is largely unknown. In this study, we aimed to investigate NMDAR dynamics and FosB/Delta FosB levels in multiple brain regions and whether they are related in sensitive brain regions during morphine abstinence. Quantitative immunohistochemistry was adopted to test NMDAR and FosB/Delta fosB levels during morphine withdrawal in rats. Increased NMDAR and FosB/Delta FosB levels were found in the nucleus accumbens core (AcbC), nucleus accumbens shell (AcbSh), central amygdaloid nucleuscapsular part (CeC), ventral tegmental area (VTA) and cingulate cortex (Cg). Double-immunofluorescence labeling indicated that NMDAR colocalized with Fos/Delta FosB in these five regions. These results suggest that multiple phenotypic regions are mediated by NMDAR and Fos/Delta FosB during morphine withdrawal, such as the motivational (AcbC, AcbSh), limbic (CeC, VTA) and executive (Cg) system pathways, and may be the primary targets of NMDAR and Fos/Delta fosB that impact morphine withdrawal behaviors. (C) 2016 Published by Elsevier Ireland Ltd.