Abstract
In a rat model of context-induced relapse to heroin, we identified sparsely distributed ventral medial prefrontal cortex (mPFC) neurons that were activated by the heroin-associated context. Selective pharmacogenetic inactivation of these neurons inhibited context-induced drug relapse. A small subset of ventral mPFC neurons formed neuronal ensembles that encode the learned associations between heroin reward and heroin-associated contexts; re-activation of these neuronal ensembles by drug-associated contexts during abstinence provoked drug relapse.
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Acknowledgements
We thank B. Navarre and K. Wihbey for their help in conducting the experiments and thank M. van den Oever for the CamKII and GAD67 immunofluorescence protocol. We also thank M. Heilig for helpful comments on the manuscript. This work was supported by the Intramural Research Program of the National Institute on Drug Abuse (US National Institutes of Health, Department of Health and Human Services).
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J.M.B. designed the experiments, ran the experiments and wrote the paper. A.L.S. ran the experiments, managed the data and made the figures. F.R.M.T. and C.C. helped perform the behavioral experiments and the molecular assays. E.K. and B.T.H. provided input on experimental design and the writing of the manuscript, and helped carry out the Daun02 inactivation experiment and the molecular assays. Y.S. supervised the project, designed the experiments and wrote the paper with J.M.B.
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Bossert, J., Stern, A., Theberge, F. et al. Ventral medial prefrontal cortex neuronal ensembles mediate context-induced relapse to heroin. Nat Neurosci 14, 420–422 (2011). https://doi.org/10.1038/nn.2758
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DOI: https://doi.org/10.1038/nn.2758
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