Morphine Tolerance as Habituation

We propose that the development of drug tolerance is congruent with the behavioral characteristics of habituation. Specifically, we show that morphine tolerance development conforms to Wagner's priming model of habituation. Tolerance develops through both associational and nonassociational routes; We attribute associational tolerance development to retrieval-generated priming of memory, whereas nonassociational tolerance we attribute to self-generating priming. This model accounts for the effects of the following on tolerance development: dose level, drug signaling, and interdose interval. Also, an habituation model is consistent with data showing that dose level and interdose interval affect the impact of drug signals on tolerance development.