Tolerance to the hyperthermic effect of morphine in the rat is a learned response.

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Abstract
The hyperthermic effect of morphine in rats becomes attenuated over the course of successive administrations by a conditional, compensatory, hypothermic response elicited by cues present at the time of morphine administration, accounting for hyperthermic tolerance. Rats with a history of morphine administration displayed a tolerant response to the hyperthermic effect of the drug and a compensatory hypothermia following a placebo if these substances were administered following cues that previously signaled morphine. Neither the tolerant reaction to morphine nor the hypothermic response to the placebo resulted when animals were injected following cues that previously signaled injection of physiological saline. Presenting environmental cues previously associated with morphine, but without the drug, abolished established tolerance, i.e., pyretic tolerance can be extinguished. Placebo sessions interspersed between morphine sessions impeded the acquisition of tolerance, i.e., pyretic tolerance was retarded by partial reinforcement. A Pavlovian conditioning process in hyperthermic tolerance was discussed. Tolerance models that do not attribute any role to drug-associated environmental cues in the acquisition of tolerance were discussed.