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Targeting the subthalamic nucleus in a preclinical model of alcohol use disorder

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Abstract

Background

The subthalamic nucleus (STN) has only recently been considered to have a role in reward processing. In rats, inactivation of the STN by lesion or high-frequency stimulation (HFS) decreases motivation for cocaine but increases motivation for sucrose. For ethanol, the effect of STN lesion depends on the individual’s baseline intake; decreasing motivation for ethanol in rats with lower ethanol intake, while increasing motivation for ethanol in rats with higher—but still limited—ethanol intake. However, the involvement of the STN in behaviour more closely resembling some aspects of alcohol use disorder has not been assessed. This study aimed to determine the effect of STN lesions on the escalation of ethanol intake, subsequent increases in the motivation to “work” for ethanol and the choice of ethanol over a non-drug alternative.

Results

We found that STN lesion prevented increases in ethanol intake observed during intermittent ethanol access and after a long period of ethanol privation. STN lesion also decreased the motivation to work for ethanol after escalated intake. Surprisingly, STN lesion increased the choice of alcohol over saccharin. This was associated with a blunting of the hedonic responses to the taste of the reinforcement alternatives.

Conclusion

These results evidence the involvement of the STN in different ethanol-motivated behaviours and therefore position the STN as an interesting target for the treatment of alcohol use disorders.

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Acknowledgements

This study has been supported by Centre National de la Recherche Scientifique, Aix-Marseille Université, Institut de Recherche et d’Etude sur les Boissons, Agence Nationale de la Recherche (Grant ANR-09-MNPS-028-01), ANR Grant 2010-NEUR-005-01 in the framework of the ERA-Net NEURON), Fondation pour la Recherche Medicale (DPA20140629789). CB and YP declare having no competing financial interests.

The authors would like to thank Brendan Tunstall for his helpful comments on the manuscript.

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Authors and Affiliations

  1. Institut de Neurosciences de la Timone, UMR7289, CNRS & Aix-Marseille Université, 27, Boulevard Jean Moulin, 13005, Marseille, France

    Yann Pelloux & Christelle Baunez

  2. National Institute on Drug Abuse Intramural Research Program, 51 Bayview Blvd #200, Baltimore, MD, 21224, USA

    Yann Pelloux

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  1. Yann Pelloux
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  2. Christelle Baunez
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Correspondence to Yann Pelloux.

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Pelloux, Y., Baunez, C. Targeting the subthalamic nucleus in a preclinical model of alcohol use disorder. Psychopharmacology 234, 2127–2137 (2017). https://doi.org/10.1007/s00213-017-4618-5

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  • DOI: https://doi.org/10.1007/s00213-017-4618-5

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