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Possible False Negative Results in Conditioned Place Preference Induced by Low-dose Morphine in Mice

Shigeru Watanabe

Conditioned Place Preference (CPP) is an easy-to-run experiment that is widely used to detect the reinforcing property of drugs. Most CPP experiments have employed post-training tests without drug injection. Here, a post-training test with drug injection was employed. C57/BL6 mice received CPP training with 0.3 mg/Kg or 3.0 mg/Kg morphine and were then tested three times: without morphine, with 0.3 mg/Kg morphine, and with 3.0 mg/Kg morphine. The mice trained with 0.3 mg/Kg did not show a significant increase in staying time at the drug-associated compartment in the drug-free test, but a significant increase was found in tests with the drug. The mice trained with 3.0 mg/Kg morphine showed conditioned preference in all tests and displayed enhancement of the conditioned preference in tests with the drug. The animals experienced environmental cues under the influence of the drug during the CPP training but were exposed to cues without the drug in the drug-free test. Thus negative results obtained in the post-training drug-free test may have been caused by differences in the stimuli the animals experienced.