Targeting the subthalamic nucleus in a preclinical model of alcohol use disorder
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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.
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.
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.
KeywordsBasal ganglia Emotion Ethanol Motivation Choice
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.
- American Psychiatric Association (2013) Diagnostic and statistical manual of mental disorders, 5th edn. American Psychiatric Association, WashingtonGoogle Scholar
- Damasio A.R., 2000. The feeling of what happens: body and emotion in the making of consciousness. Harcourt; New York.Google Scholar
- Lévêque M, Carron R, Régis JM (2013) Radiosurgery for the treatment of psychiatric disorders: a review. World Neurosurg 80(3–4):S32.e1–S32.e9Google Scholar
- Li N, Wang J, Wang XL, Chang CW, Ge SN, Gao L, Wu HM, Zhao HK, Geng N, Gao GD (2012) Nucleus accumbens surgery for addiction. World Neurosurg 80(3–4):S28.e9–S28.19Google Scholar
- Paxinos G, Watson C (2005) The rat brain in stereotaxic coordinates, 5th edn. Academic, San DiegoGoogle Scholar
- Paxinos G, Watson C (2013) The rat brain in stereotaxic coordinates, 7th edn. Academic Press, CambridgeGoogle Scholar
- Pelloux Y, Meffre J, Giorla E, Baunez C (2014) The subthalamic nucleus keeps you high on emotion: behavioral consequences of its inactivation. Front Behav Neurosci 5(8):414Google Scholar
- Richter CP (1940) Alcohol as food. Quarterly Journal of Studies on Alcoholism 1:650–661Google Scholar
- Wade CL, Kallupi M, Hernandez DO, Breysse E, de Guglielmo G, Crawford E, Koob GF, Schweitzer P, Baunez C, George O (2017) High-frequency stimulation of the subthalamic nucleus blocks compulsive-like re-escalation of heroin taking in rats. Neuropsychopharmacology. doi: 10.1038/npp.2016.270