Pavlovian conditioning and addictive behavior: relapse to oral self-administration of morphine.

The effect of conditional environmental stimuli on morphine consumption in rats was examined. Rats were first trained to consume a morphine solution (increased from 0.5 mg/ml to 1.2 mg/ml) by a forced drinking procedure spanning 235 days. Then, a period of abstinence of 81 days was given. They next received injections of morphine in one environment and injections of saline in a different environment (30 injections of morphine, dose increased from 5 mg/kg to 40 mg/kg). At the end of this phase, the effects of conditional environmental stimuli on tolerance to the analgesic effect of 40 mg/kg morphine were examined. Consistent with previous results, analgesic tolerance was most pronounced in the context of the cues previously associated with subcutaneous morphine injections. Finally, the effects of the different environments on consumption of morphine were determined in one-bottle and two-bottle tests. In a two-bottle test, there was almost no consumption of the morphine solution regardless of environment. In a one-bottle test, significantly more morphine was consumed in the drug environment than in the saline environment. The results are discussed in relation to theoretical views of the role of environmental stimuli in tolerance and drug dependence.