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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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).
Conflict of interest
The authors declare that they have no conflict of interest.
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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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