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Altered neuronal activity in the ventromedial prefrontal cortex drives nicotine intake escalation

Neuropsychopharmacology volume 48, pages 887–896 (2023)Cite this article

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Abstract

Nicotine addiction develops after prolonged drug use and escalation of drug intake. However, because of difficulties in demonstrating escalation of nicotine use in rats, its underlying neuroadaptations still remain poorly understood. Here we report that access to unusually high doses of nicotine (i.e., from 30 µg to 240 µg/kg/injection) for self-administration precipitated a rapid and robust escalation of nicotine intake and increased the motivation for the drug in rats. This nicotine intake escalation also induced long-lasting changes in vmPFC neuronal activity both before and during nicotine self-administration. Specifically, after escalation of nicotine intake, basal vmPFC neuronal activity increased above pre-escalation and control activity levels, while ongoing nicotine self-administration restored these neuronal changes. Finally, simulation of the restoring effects of nicotine with in vivo optogenetic inhibition of vmPFC neurons caused a selective de-escalation of nicotine self-administration.

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Fig. 1: Nicotine intake escaladed with increasing doses of nicotine.
Fig. 2: Nicotine escalation induced convulsive-like behavior.
Fig. 3: Changes in vmPFC neuronal activity during nicotine intake escalation.
Fig. 4: In vivo optogenetic inhibition of vmPFC decreased nicotine self-administration.
Fig. 5: In vivo optogenetic inhibition of vmPFC had no effect on sucrose self-administration.

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Funding

This work was supported by the French Research Council (CNRS), the Université de Bordeaux, and the French National Agency (ANR- 15-CE37-0008-01; KG). The authors have nothing to disclose.

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  1. These authors contributed equally: Myriam Abarkan, Giulia R. Fois.

Authors and Affiliations

  1. Université de Bordeaux, CNRS, Chimie et Biologie des Membranes et Nano-objets, UMR, 5248, Pessac, France

    Myriam Abarkan

  2. Université de Bordeaux, CNRS, INCIA, UMR 5287, F-33000, Bordeaux, France

    Giulia R. Fois, Caroline Vouillac-Mendoza, Serge H. Ahmed & Karine Guillem

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Contributions

KG and SHA designed research and experiments; CVM, KG, and MA performed behavioral experiments and associated data analysis; GRF and KG performed in vivo electrophysiology and optogenetic experiments, and associated data analysis; GRF performed immunohistochemistry; KG and SHA wrote the paper.

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Correspondence to Karine Guillem.

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Abarkan, M., Fois, G.R., Vouillac-Mendoza, C. et al. Altered neuronal activity in the ventromedial prefrontal cortex drives nicotine intake escalation. Neuropsychopharmacol. 48, 887–896 (2023). https://doi.org/10.1038/s41386-022-01428-9

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