Central interaction of dexamethasone and RU-38486 on morphine antinociception in mice

The central interference induced by dexamethasone and RU-38486, (a glucocorticoid receptor antagonist) on morphine antinociception were studied by using the tail flick test in mice. Dexamethasone, injected intracerebrally (i.c.v.) 10 minutes before morphine, dose-dependently reduced morphine antinociception, whereas RU-38486 which was injected with the same lag time, potentiated it. When dexamethasone and RU-38486 were administered together i.c.v., 10 minutes before morphine, an overall reduction of morphine antinociception was observed, similar to that observed with dexamethasone pretreatment only. The present results strongly suggest a central site of interaction for dexamethasone and RU-38486 on morphine antinociception; the short latency and the dose-related slope for this interaction may suggest a mechanism at least in part different from the glucocorticoid-induced genomic activation.