Effects of dose, interdose interval, and drug-signal parameters on morphine analgesic tolerance: implications for current theories of tolerance.

Some unique predictions of a dual-process priming model of morphine analgesic tolerance were tested. Two experiments in which morphine injections during a tolerance acquisition phase were accompanied by nociceptive testing on a hot plate, confirmed the predictions that tolerance acquisition, retention, and environment-specificity would be augmented under signaled drug conditions when low doses or long interdose intervals (IDIs) were used but not when high doses or short IDIs were used. The implications for current alternative theories of morphine tolerance are discussed.