Persistence and drug-induced reinstatement of a morphine-induced conditioned place preference

Morphine induces a conditioned place preference (CPP) for a chamber associated with the drug. In the present set of experiments, we explored the persistence, extinction, and reinstatement of a morphine-induced CPP using an 'unbiased' apparatus with two distinct chambers separated by a smaller neutral zone. Rats were given four 45 min pairings of one chamber with morphine (Experiments 1 and 2: 1.0, 5.0, or 10.0 mg/kg, s.c.; Experiments 3A and 3B: 10.0 mg/kg, s.c.) and four pairings of the other chamber with saline on alternate days. Following conditioning, rats were given 15 min tests for chamber preference. In Experiment 1, rats showed a CPP following conditioning with all doses. In Experiment 2, in the same animals, the CPP was evident in subsequent tests given either 2 or 6 weeks following the initial test for preference. Furthermore, in the animals tested 2 weeks after the initial CPP test, the CPP was maintained for 12 weeks when tests were repeated every 2 weeks. Animals tested at 6 weeks were again tested after another 6-week delay and showed a clear preference for the previously morphine-paired chamber. In Experiment 3A, rats underwent place conditioning as above with 10.0 mg/kg morphine. Following extinction during which both chambers were paired with saline for 45 min on four occasions, the CPP was no longer evident. The CPP was reinstated by priming injections of 1.0 or 2.5 mg/kg morphine, but not 0.5 mg/kg in a 30 min test. Similar results were found in Experiment 3B, in which the CPP was reinstated following a priming injection of morphine (2.5 mg/kg) given immediately or 15 min before a 30 min test; no reinstatement was seen after injections of saline. These results show that a morphine-induced CPP is persistent over time and can be reinstated by morphine after extinction.