Clonidine-induced antinociception and locomotor hypoactivity are reduced by dexamethasone in mice

The effects of dexamethasone pretreatment on clonidine-induced antinocicept ion and locomotor hypoactivity were investigated in mice. In the hot-plate and the tail-flick tests, dexamethasone administered intraperitoneally at a dose of 1 mg kg(-1), 30 or 60 min before clonidine, reduced clonidine anti nociception in both tests and reduced clonidine-induced locomotor hypoactiv ity in the activity cage. When administered 15 min before clonidine, dexame thasone had no effect on clonidine antinociception. A higher dexamethasone dose (10 mg kg(-1)) induced the same effects observed at a dose of 1 mg kg( -1) in the hot-plate and the tail-flick tests, but the former dose had a st ronger effect on locomotor hypoactivity. Dexamethasone (10 ng/mouse) admini stered intracerebroventricularly 30 min before clonidine was also able to r educe both clonidine-induced antinociception and locomotor hypoactivity. Th e protein synthesis inhibitor, cycloheximide, administered intraperitoneall y at the dose of 10 mg kg(-1). 2 h before clonidine, was able to prevent de xamethasone effects on clonidine induced antinociception. The glucocorticoi d receptor antagonist RU-38486, administered intracerebroventricularly at t he dose of 1 ng/mouse, was also able to block dexamethasone effects on clon idine-induced antinociception and locomotor hypoactivity, whereas both cycl oheximide and RU-38486 per se did not influence pain sensitivity or locomot or activity. These results suggest: that the dexamethasone effects on cloni dine-induced antinociception and locomotor hypoactivity depend on the stimu lating effects that dexamethasone exert, on the protein synthesis via the g lucocorticoid receptor in the brain.