Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Brief Communication
  • Published:

Ventral medial prefrontal cortex neuronal ensembles mediate context-induced relapse to heroin

Subjects

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.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Context-induced reinstatement of heroin seeking is associated with Fos induction in dorsal and ventral mPFC (dmPFC and vmPFC).
Figure 2: Nonselective global inhibition of the majority of ventral, but not dorsal, mPFC neurons by muscimol and baclofen decreased context-induced reinstatement of heroin seeking.
Figure 3: Ventral mPFC Daun02 injections after exposure to the heroin-associated context during induction day decreased subsequent context-induced reinstatement of heroin seeking.

Similar content being viewed by others

References

  1. Wikler, A. Arch. Gen. Psychiatry 28, 611–616 (1973).

    Article  CAS  Google Scholar 

  2. Bouton, M.E. & Bolles, R.C. Learn. Motiv. 10, 445–466 (1979).

    Article  Google Scholar 

  3. Crombag, H., Bossert, J.M., Koya, E. & Shaham, Y. Philos. Trans. R. Soc. Lond. B Biol. Sci. 363, 3233–3243 (2008).

    Article  Google Scholar 

  4. Peters, J., Kalivas, P.W. & Quirk, G.J. Learn. Mem. 16, 279–288 (2009).

    Article  Google Scholar 

  5. Van den Oever, M.C. et al. Nat. Neurosci. 11, 1053–1058 (2008).

    Article  CAS  Google Scholar 

  6. Rogers, J.L., Ghee, S. & See, R.E. Neuroscience 151, 579–588 (2008).

    Article  CAS  Google Scholar 

  7. Hebb, D.O. The Organization of Behavior (Wiley, New York, 1949).

  8. Pennartz, C.M., Groenewegen, H.J. & Lopes da Silva, F.H. Prog. Neurobiol. 42, 719–761 (1994).

    Article  CAS  Google Scholar 

  9. Eichenbaum, H. Science 261, 993–994 (1993).

    Article  CAS  Google Scholar 

  10. Koya, E. et al. Nat. Neurosci. 12, 1069–1073 (2009).

    Article  CAS  Google Scholar 

  11. Kasof, G.M. et al. J. Neurosci. 15, 4238–4249 (1995).

    Article  CAS  Google Scholar 

  12. Bossert, J.M., Poles, G.C., Wihbey, K.A., Koya, E. & Shaham, Y. J. Neurosci. 27, 12655–12663 (2007).

    Article  CAS  Google Scholar 

  13. Peters, J., LaLumiere, R.T. & Kalivas, P.W. J. Neurosci. 28, 6046–6053 (2008).

    Article  CAS  Google Scholar 

  14. Celentano, M. et al. Psychopharmacology (Berl.) 204, 349–360 (2009).

    Article  CAS  Google Scholar 

  15. Ettenberg, A., Pettit, H.O., Bloom, F.E. & Koob, G.F. Psychopharmacology (Berl.) 78, 204–209 (1982).

    Article  CAS  Google Scholar 

Download references

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).

Author information

Authors and Affiliations

Authors

Contributions

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.

Corresponding author

Correspondence to Yavin Shaham.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–3 (PDF 233 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nn.2758

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing