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.
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Acknowledgments
We would like to thank Yu Shen for helpful comments on the manuscript. The study was supported by funds from the National Natural Science Research Foundation of China (NSFC: 30870802, 30711120564) and National Program of Basic Research sponsored by the Ministry of Science and Technology of China (2009CB522002).
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The authors declare no competing financial interests.
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Xiang Ma and Jianjun Zhang contributed equally to this work.
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Ma, X., Zhang, JJ. & Yu, LC. Post-retrieval extinction training enhances or hinders the extinction of morphine-induced conditioned place preference in rats dependent on the retrieval-extinction interval. Psychopharmacology 221, 19–26 (2012). https://doi.org/10.1007/s00213-011-2545-4
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DOI: https://doi.org/10.1007/s00213-011-2545-4