Post-retrieval extinction training enhances or hinders the extinction of morphine-induced conditioned place preference in rats dependent on the retrieval-extinction interval

Drug-associated memories are hypothesized to underlie the high risk of relapse in addiction. Recent studies show that post-retrieval extinction training erases fear memories by reconsolidation blockade. Here, we examine the efficacy of this non-invasive procedure in rats with drug-associated memories and explore the underlying mechanisms by varying retrieval-extinction intervals. To confirm the erasure hypothesis, in addition to the conventional spontaneous recovery and reinstatement assays, we conduct further assessment to detect the existence of drug-associated memories. Morphine-induced conditioned place preference (CPP) model in rats was used to examine the effects of post-retrieval extinction training. After the establishment of morphine-induced CPP, CPP testing was used to retrieve drug-associated memories. In the following extinction training session, two groups of rats received conventional extinction training, that is, confined extinction training or repeated testing daily; the other two groups of rats underwent confined extinction training 10 min or 3 h after CPP testing, daily. The recoverability of the extinguished CPP was examined by spontaneous recovery and reinstatement assays. Post-retrieval extinction training with a 10-min retrieval-extinction interval facilitated CPP extinction and suppressed the reinstatement and spontaneous recovery of extinguished CPP; nevertheless, CPP returned in the reinstatement assay after the 4-week spontaneous recovery test. In contrast, post-retrieval extinction training with a 3-h retrieval-extinction interval retarded the extinction of CPP. These results demonstrate that post-retrieval extinction training can either improve or impair CPP extinction depending on the retrieval-extinction interval.