Morphine tolerance in rats: congruence with a Pavlovian paradigm

Evidence for associational and nonassociational mechanisms of tolerance development was found in four experiments using an automated flinch/jump assessment of morphine's analgesic effects. Rats receiving morphine in a distinctive environment displayed greater tolerance when tested in that environment than animals receiving equal but unpaired exposure to the drug and environment. This context effect occurred at low (5 mg/kg) and moderate (20 mg/kg) doses and was attenuated by predrug exposure to the tolerance-test environment. This attenuation was found to be due to latent inhibition rather than to stress induction or novelty reduction. In general, results of this series of experiments support a Pavlovian model of contextually mediated tolerance and are inconsistent with other explanations.