Expression of metabotropic glutamate receptor 5 in spinal cord of morphine tolerant rats

Abstract

To investigate the expression of metabotropic glutamate receptor 5 (mGluRS) in spinal cord of morphine tolerant rats and understand the influence of mGluR5 antagonist MPEP upon the expression of mGluRS. Male Sprague-Dawley rats were randomly divided into four groups with 8 rats each:control group (NS), morphine group, morphine plus MPEP group and MPEP group. A morphine tolerance model of rat was established by repeated administration of 10 microg morphine intrathecally twice daily for 7 days. The effects of morphine co-administrated with MPEP upon the thermal pain threshold were examined by tail flick test. Tail flick latency (TFL) was measured at 30 min pre- and postdosing. MPE% (percentage of maximal possible effect) was calculated by the equation: MPE (%) = [(test response time-basal response time)/(cut-off time-basal response time)] x 100%. The rats were sacrificed and L4-5 spinal cord tissue was removed. The expression of mGluR5 in every group was examined by immunofluorescence and Western blot. MPE% of morphine group decreased gradually after chronic administration of morphine intrathecally. There was no significant difference between morphine group and control group at Day 7 (P > 0.05). Morphine plus MPEP group had significant analgesic effect as compared with morphine group at Day 7 (P < 0.05). The expression of mGluR5 was up-regulated in the dorsal horn of spinal cord in morphine tolerant rats. The protein level of mGluRS in morphine plus MPEP group was lower than that in morphine group (P < 0.05), but higher than control group (P < 0.05). The mGluR5 antagonist MPEP can prevent the development of morphine tolerance. The expression of mGluR5 protein increases in the spinal cord of morphine tolerant rats. MPEP plays its role in morphine tolerance by partly inhibiting the expression of mGluRS.