Pro-Leu-Gly-NH2 serves as a conditioned stimulus in the acquisition of conditioned tolerance.

The effect of Pro-Leu-Gly-NH2 (MIF) on the acquisition of tolerance to morphine-induced antinociception and its efficacy as a cue predictive of morphine administration was examined. Daily administration of MIF prior to morphine injection did not attenuate the acquisition of tolerance to the antinociceptive properties of morphine, as measured by the latency to hindpaw lick in a hot-plate test of analgesia. When the animals were tested 72 hr later without MIF pretreatment, they appeared to lose tolerance, as indicated by longer latencies to paw lick. These data suggest that in some situations MIF may interfere with the acquisition of tolerance by acting as a cue that reliably predicts the antinociceptive properties of morphine.