A new place conditioning paradigm to study tolerance to opiates in mice.

Tolerance to the rewarding properties of morphine was investigated in mice using a new conditioned place preference (CPP) procedure. Four pairings of morphine with specific environmental cues induced a significant CPP for the drug-paired cues. Further opiate conditioning trials in the presence of the same environmental cues revealed no change in the drug-induced CPP on repeated test sessions. Subsequent exposure of the same animals to conditioning trials by pairing morphine with a set of novel environmental cues showed that the opiate was still able to produce a CPP in mice treated with a total of 16 morphine injections. The present CPP paradigm may prove useful to investigate tolerance to the rewarding properties of drugs of abuse.