Morphine's interoceptive stimuli as cues for the development of associative morphine tolerance in the rat

Abstract

This study examined the extent to which a 4-mg/kg dose of morphine paired explicitly with a 12 mg/kg dose could gain associative control over tolerance development in rats. The analgesic effects of morphine were measured on the tail-flick test. Tolerance was defined as the dose shift to the right of the dose-response curve (DRC) of drug-experience animals relative to saline control animals. DRC shifts to the right were greater in the explicitly paired than in the explicitly unpaired animals. The results suggest that the pharmacological effects of morphine may function as a conditioned stimulus for the development of associative morphine tolerance.