Timing of cycloheximide administration and inhibition of the development of analgesic tolerance to morphine.

A single injection of cycloheximide (10 mg/kg, i.p.) partially prevented the development of analgesic tolerance to morphine (10 mg/kg, i.p. daily for 5 days). The inhibitory effect of cycloheximide was strictly dependent on the time of its administration, and only effective when it was administered 2 hrs before or 1 hr after morphine injection. Daily repeated treatment with cycloheximide 2 hrs before and/or 1 hr after morphine also prevented the tolerance development. However, the pre or post treatment with cycloheximide differed in the duration of the effect, and the discrepancies between two treatments suggest the importance of timing of the administration of inhibitor in the underlying mechanisms.