Blocking and sensory preconditioning effects in morphine analgesic tolerance: Support for a pavlovian conditioning model of drug tolerance

Two experiments on rats tested predictions of a Pavlovian conditioning model of drug tolerance which holds that tolerance is the result of compensatory conditioned responses, developed to environmental stimuli accompanying the drug administrations, which attenuate the direct effects of the drug. In Experiment I, the acquisition of tolerance-modulating properties by the tone component of a tone-light compound stimulus which accompanied morphine administrations was reduced by prior light-morphine pairings (blocking). In Experiment II, a tone stimulus acquired tolerance-modulating properties through prior pairings with a light stimulus which later accompanied morphine administrations (sensory preconditioning). These findings are uniquely predicted by the Pavlovian conditioning model of drug tolerance and are incompatible with traditional theories which assign no role to environmental stimuli present at the time of drug administration.