A complete analysis of NMDA receptor subunits in periaqueductal grey and ventromedial medulla of morphine tolerant mice.

Behavioral studies indicate that the inhibition of glutamatergic system with antagonists of ionotropic glutamate NMDA receptors (NMDA-Rs) during long term morphine administration inhibits the development of morphine tolerance and dependence. In the present study we investigated whether chronic morphine treatment leading to the development of morphine antinociceptive tolerance as observed in tail-flick test in mice, may affect the expression of NMDA-R subunits. The expression of NMDA-R subunits was examined in brain areas mediating nociceptive signaling and responsible for antinociceptive activity of morphine. These included periaqueductal grey matter (PAG) and rostral ventromedial medulla (RVM). The expression of NR1 and all subunits of NR2 family (NR2A, NR2B, NR2C, NR2D) of NMDA receptor complex was examined using immunoblotting method. Although behavioral test indicated that morphine antinociceptive tolerance developed, changes in the expression of NMDA-R subunits were not observed, either in the PAG or in the RVM.