Associate and non-associative tolerance to morphine: support for a dual-process habituation model

Some unique predictions of a dual-process habituation model of morphine analgesic tolerance were examined concerning the interactions of drug-signal conditions and dose/frequency parameters. The model assumes that tolerance is the result of a combination of associative and non-associative habituation mechanisms which are differentially affected by dose and drug-signal conditions. In accordance with predictions of the model, low doses and long interdrug intervals (IDI's) resulted in faster tolerance acquisition, greater tolerance retention, and higher levels of associative tolerance, than high doses and short IDI's. Alternative accounts of tolerance based on Pavlovian conditioning mechanisms cannot explain this pattern of results. The question of generality of these findings to other drugs and other response measures is discussed.