Clonidine-induced antinociception and locomotor hypoactivity are reduced by dexamethasone in mice.
The effects of dexamethasone pretreatment on clonidine-induced antinociception 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 antinociception in both tests and reduced clonidine-induced locomotor hypoactivity in the activity cage. When administered 15 min before clonidine, dexamethasone 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 stronger effect on locomotor hypoactivity. Dexamethasone (10 ng/mouse) administered intracerebroventricularly 30 min before clonidine was also able to reduce both clonidine-induced antinociception and locomotor hypoactivity. The protein synthesis inhibitor, cycloheximide, administered intraperitoneally at the dose of 10 mg kg(-1), 2 h before clonidine, was able to prevent dexamethasone effects on clonidine-induced antinociception. The glucocorticoid receptor antagonist RU-38486, administered intracerebroventricularly at the dose of 1 ng/mouse, was also able to block dexamethasone effects on clonidine-induced antinociception and locomotor hypoactivity, whereas both cycloheximide and RU-38486 per se did not influence pain sensitivity or locomotor activity. These results suggest that the dexamethasone effects on clonidine-induced antinociception and locomotor hypoactivity depend on the stimulating effects that dexamethasone exert, on the protein synthesis via the glucocorticoid receptor in the brain.
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Department of Pharmaceutical Sciences, University of Salerno, Fisciano, Italy. annacap@unisa.it
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D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D018712:Analgesics, Non-Narcotic / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D003000:Clonidine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D003907:Dexamethasone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D010147:Pain Measurement / Q000187:drug effects; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011930:Reaction Time / Q000187:drug effects; D015016:Yohimbine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D018712:Analgesics, Non-Narcotic; D000893:Anti-Inflammatory Agents; D011500:Protein Synthesis Inhibitors; D015016:Yohimbine; D003907:Dexamethasone; D003513:Cycloheximide; D003000:Clonidine