Clonidine analgesia: tolerance and cross-tolerance to autoanalgesia.

Clonidine induced significant antinociception in rats, as assessed by radiant-heat tail-flick procedures. Continued administration of 0 5 mg/kg and 1.0 mg/kg of the drug for 7 days induced significant analgesic tolerance in a dose-dependent manner. Significant cross-tolerance to antinociception elicited by acute footshock or classical conditioning procedures was observed, with the greatest cross-tolerance being exhibited by the 1.0 mg/kg group. These data suggest similar noradrenergic mechanisms may subserve clonidine antinociception and autoanalgesia.