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Subthalamic nucleus high frequency stimulation prevents and reverses escalated cocaine use

Molecular Psychiatry volume 23, pages 2266–2276 (2018)Cite this article

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Abstract

One of the key features of addiction is the escalated drug intake. The neural mechanisms involved in the transition to addiction remain to be elucidated. Since abnormal neuronal activity within the subthalamic nucleus (STN) stands as potential general neuromarker common to impulse control spectrum deficits, as observed in obsessive–compulsive disorders, the present study recorded and manipulated STN neuronal activity during the initial transition to addiction (i.e., escalation) and post-abstinence relapse (i.e., re-escalation) in rats with extended drug access. We found that low-frequency (theta and beta bands) neuronal oscillations in the STN increase with escalation of cocaine intake and that either lesion or high-frequency stimulation prevents the escalation of cocaine intake. STN–HFS also reduces re-escalation after prolonged, but not short, protracted abstinence, suggesting that STN–HFS is an effective prevention for relapse when baseline rates of self-administration have been re-established. Thus, STN dysfunctions may represent an underlying mechanism for cocaine addiction and therefore a promising target for the treatment of addiction.

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Acknowledgements

The authors thank Drs. P Carrieri, C Bernard, P Belin, F Brocard, and G Masson for critical reading of the manuscript and the technical support from J. Baurberg and animal facilities personal. This research was funded by CNRS, Aix-Marseille Université (AMU), the “Agence Nationale pour la Recherche” (ANR_2010-NEUR-005-01 in the framework of the ERA-Net NEURON to CB and supporting to YP), the Fondation pour la Recherche Médicale (FRM DPA20140629789 to CB), National Institutes of Health grants DA (DA029821 to GFK) from the National Institute on Drug Abuse and the Fondation de l’Avenir (ET2-655 to CB).

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Author notes

  1. Yann Pelloux

    Present address: Department of Neuroscience and Physiology, Neuroscience Institute, New York University Medical Center, New York, NY, 10016, USA

  2. These authors contributed equally: Yann Pelloux, Mickaël Degoulet.

Authors and Affiliations

  1. Institut de Neurosciences de la Timone, UMR 7289 CNRS & Aix-Marseille Université, 27 Bld J. Moulin, F-13000, Marseille, France

    Yann Pelloux, Mickaël Degoulet, Alix Tiran-Cappello, Candie Cohen, Sylvie Lardeux & Christelle Baunez

  2. Département de Biologie, Ecole Normale Supérieure de Lyon, 69007, Lyon, France

    Alix Tiran-Cappello

  3. Department of Neuroscience, The Scripps Research Institute, La Jolla, CA, USA

    Olivier George & George F. Koob

  4. Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, 146 rue Léo-Saignat, F-33000, Bordeaux, France

    Serge H. Ahmed

  5. CNRS, Institut des Maladies Neurodégénératives, UMR 5293, 146 rue Léo-Saignat, F-33000, Bordeaux, France

    Serge H. Ahmed

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Pelloux, Y., Degoulet, M., Tiran-Cappello, A. et al. Subthalamic nucleus high frequency stimulation prevents and reverses escalated cocaine use. Mol Psychiatry 23, 2266–2276 (2018). https://doi.org/10.1038/s41380-018-0080-y

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