Maintenance of conditioned place preferences and aversion in C57BL6 mice: effects of repeated and drug state testing

In order to determine the factors affecting the expression of place conditioning (i.e. conditioned place preference or aversion), groups of C57BL6 mice were conditioned to morphine, cocaine or naloxone (all drugs 4 mg/kg s.c.) and tested intermittently (up to 4 weeks) or repeatedly (daily). When tested once only in a drug-free state, the expression of place conditioning to all drugs generally strengthened with the passing of time and was only marginally different when tested once more later. The expression of place conditioning was remarkably resistant to extinction during repeated daily testing, though decreases were observed over 2 weeks of testing. Subsequently, a small and non-significant degree of spontaneous recovery of the expression of place conditioning was observed when animals were undisturbed for an extended period of time. Administering animals the same drug to which they were conditioned 20 min prior to testing (i.e. drug state testing), either prior to or following repeated testing, enhanced expression of morphine-induced conditioned place preference, whereas expression of cocaine-induced conditioned place preference was unaffected. When vehicle was administered prior to testing, there was no evidence of naloxone-induced conditioned place aversion, whereas naloxone administration maintained conditioned place aversion. These results show that the expression of place conditioning in C57BL6 mice does not readily diminish over time, but on the contrary, tends to strengthen if tested only once or intermittently. Thus, the hedonic properties of drugs may be more clearly revealed during long-term, rather than short-tem testing, and in some instances, when tested in the drugged state.