The role of group III metabotropic receptors on opioid tolerance

ABSTRACT

BACKGROUND: Prolonged exposure to morphine causes tolerance to morphine-induced antinociception, yet the mechanisms of such tolerance are not fully understood. Although group I and II metabolic glutamate receptors (mGluRs) are involved in the modulation of morphine tolerance, the role of the group III mGluRs has not been determined. Therefore, we examined the effect of a group III mGluRs agonist on the morphine tolerance in the spinal cord. METHODS: An intrathecal infusion of morphine (40 nmol/microl/h) for 5 days was done to examine the development of morphine tolerance in male Sprague-Dawley rats. Noxious radiant heat was applied to the hindpaw and we measured the thermal withdrawal latency. To clarify the role of the group III mGluRs, an intrathecal group III mGluRs agonist (ACPT-III) or saline was administered to the morphine tolerant rats and we observed the change of the thermal withdrawal latency at 15, 30, 60, 90 and 120 min after delivery of ACPT-III. RESULTS: A continuous intrathecal infusion of morphine significantly increased the thermal withdrawal latency, as compared with the saline infused rats on day 1, with a decline on day 3 and the increase of withdrawal latency totally disappeared on day 5 (tolerance). Intrathecal ACPT-III increased the thermal withdrawal latency in the morphine tolerance rats. CONCLUSIONS: These results suggest that the group III mGluRs may be involved in the suppression of tolerance to morphine-induced antinociception at the spinal level.