Xiang Ma1, Jian-Jun Zhang, Long-Chuan Yu. 1. Laboratory of Neurobiology and State Key Laboratory of Biomembrane and Membrane Biotechnology, College of Life Sciences, Peking University, Beijing 100871, People's Republic of China.
Abstract
RATIONALE AND OBJECTIVE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: These results demonstrate that post-retrieval extinction training can either improve or impair CPP extinction depending on the retrieval-extinction interval.
RATIONALE AND OBJECTIVE: 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. MATERIALS AND METHODS: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. RESULTS: 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. CONCLUSION: These results demonstrate that post-retrieval extinction training can either improve or impair CPP extinction depending on the retrieval-extinction interval.