Influence of stress on morphine-induced hyperthermia: relevance to drug conditioning and tolerance development.

Controversy exists regarding (a) whether rats become tolerant, or sensitized, to morphine-induced hyperthermia and (b) the directionality of the conditioned pyretic effects of morphine. In these studies, stress produced by temperature-assessment procedures affected rats' pyretic response to morphine. Under conditions of high stress, rats first showed diminished, and then enhanced, hyperthermic responding across repeated morphine dosing (5 or 35 mg/kg). The diminished hyperthermia can be attributed to habituation to high levels of assessment stress. Repeated morphine doses delivered under conditions of low stress produced only enhanced hyperthermic responding, which indicates that rats become sensitized to morphine's hyperthermic effects. There was little evidence that morphine supported conditioning of pyretic responses. Finally, the temperature-assessment stress that produced hyperthermia was mediated by opiate peptides, was blocked by naloxone, and enhanced the agonist effects of morphine. The relevance of these findings to theories of drug conditioning and tolerance is discussed.