Extinction of morphine analgesic tolerance

It has been suggested that the analgesic effect of morphine becomes attenuated over the course of successive administrations by a conditional, compensatory, hyperalgesic response elicited by the administration procedure, thus accounting (in part) for analgesic tolerance. On the basis of this associative model of tolerance, it would be predicted that established tolerance would be extinguished by placebo sessions. In experiments of apparently similar design (but conducted by different experimenters in different laboratories), data both confirming and refuting this prediction have previously been published. The present experiment, conducted jointly by the experimenters who reported the divergent findings, was designed to determine the reasons for the different results. It was found that placebo sessions do consistently attenuate morphine analgesic tolerance. Such extinction is not limited to the experimenter, drug preparation, rat strain, or apparatus used in the original, successful demonstration of the phenomenon, but rather is also demonstrable under conditions similar to those used in subsequent experiments which failed to demonstrate extinction of tolerance. Results of the present experiment suggest that the failures to demonstrate extinction of tolerance were attributable to insufficient extinction training.