Inhibitory effects of Group I metabotropic glutamate receptors antagonists on the expression of NMDA receptor NR1 subunit in morphine tolerant rats

N-Methyl-d-aspartate receptor (NMDAR) and Group I metabotropic glutamate receptors (mGluRs) are involved in the process of morphine tolerance. Previous studies have shown that Group I mGluRs can modulate NMDAR functions in the central nervous system. The aim of the present study was to examine the influence of Group I mGluRs antagonists on the expression of NMDA receptor NR1 subunit (NR1) in the rat spinal cord. Morphine tolerance was induced in rats by repeated administration of 10 μg morphine (intrathecal, i.t.) twice a day for 7 consecutive days. Tail flick test was used to assess the effect of Group I mGluRs antagonist, AIDA ((RS)-1-Aminoindan-1,5 dicarboxylic acid) or mGluR5 antagonist, MPEP (2-methyl-6-(phenylethynyl)pyridine) on morphine antinociceptive tolerance. The expression of NR1 was measured by immunofluorescence and Western blot. Behavioral tests revealed that both AIDA and MPEP attenuated the development of morphine tolerance. The expression of NR1 was upregulated in the dorsal horn of spinal cord after chronic morphine treatment. AIDA or MPEP co-administered with morphine attenuated morphine induced upregulation of NR1. These findings suggest that the development of morphine tolerance partly prevented by Group I mGluRs antagonists may due to its inhibitory effect on the expression of NR1 subunit.