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The rostromedial tegmental nucleus gates fat overconsumption through ventral tegmental area output in male rats

Neuropsychopharmacology (2024)Cite this article

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Abstract

Excessive consumption of palatable foods that are rich in fats and sugars has contributed to the increasing prevalence of obesity worldwide. Similar to addictive drugs, such foods activate the brain’s reward circuit, involving mesolimbic dopaminergic projections from the ventral tegmental area (VTA) to the nucleus accumbens (NAc) and the prefrontal cortex. Neuroadaptations occurring in this circuit are hypothesized to contribute to uncontrolled consumption of such foods, a common feature of most of eating disorders and obesity. The rostromedial tegmental nucleus (RMTg), also named tail of the VTA (tVTA), is an inhibitory structure projecting to the VTA and the lateral hypothalamus (LH), two key brain regions in food intake regulation. Prior research has demonstrated that the RMTg responds to addictive drugs and influences their impact on mesolimbic activity and reward-related behaviors. However, the role of the RMTg in food intake regulation remains largely unexplored. The present study aimed to investigate the role of the RMTg and its projections to the VTA and the LH in regulating food intake in rats. To do so, we examined eating patterns of rats with either bilateral excitotoxic lesions of the RMTg or specific lesions of RMTg-VTA and RMTg-LH pathways. Rats were exposed to a 6-week ‘free choice high-fat and high-sugar’ diet, followed by a 4-week palatable food forced abstinence and a 24 h re-access period. Our results indicate that an RMTg-VTA pathway lesion increases fat consumption following 6 weeks of diet and at time of re-access. The RMTg-LH pathway lesion produces a milder effect with a decrease in global calorie intake. These findings suggest that the RMTg influences palatable food consumption and relapse through its projections to the VTA.

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Fig. 1: Neuroanatomical characterization of RMTg-VTA and RMTg-LH connectivity.
Fig. 2: Bilateral excitotoxic lesion of the RMTg modulates palatable food intake in a free choice obesogenic diet.
Fig. 3: Targeted lesion of the RMTg-VTA pathway increases fat intake, relapse and promotes locomotor activation during forced abstinence and re-access.
Fig. 4: Specific lesion of the RMTg-LH pathway decreases total food intake and influences locomotor activation during the last week of forced abstinence.

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All the data supporting the findings of this study can be provided upon request from the corresponding author.

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Acknowledgements

We thank Marion Neurdin and Adeline Coursan for their help with neuroanatomical studies, Romain Goutagny for providing retro Cre EGFP virus, Jorge Mendoza for providing the OX antibody, and Victor Mathis and Mary C. Olmstead for manuscript proofreading and fruitful discussions. We thank the PIV (Plateforme d’Imagerie in Vitro, INCI, Strasbourg) and the LNCA animal facility staff.

Funding

This project was supported by the Université de Strasbourg, the Centre National de la Recherche Scientifique (CNRS). Florian Schoukroun received a PhD fellowship from the French Ministère de l’Enseignement Supérieur et de la Recherche.

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  1. These authors contributed equally: Katia Befort, Romain Bourdy.

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  1. Laboratoire de Neurosciences Cognitives et Adaptatives (LNCA), Université de Strasbourg, UMR7364, CNRS, 12 Rue Goethe, 67000, Strasbourg, France

    Florian Schoukroun, Katia Befort & Romain Bourdy

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  1. Florian Schoukroun
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KB and RB designed the research. FS and RB performed the experiments and analyzed the data. FS, KB and RB wrote the manuscript. KB and RB prepared the revised version of the manuscript. All authors gave final approval to the manuscript.

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Correspondence to Katia Befort or Romain Bourdy.

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Schoukroun, F., Befort, K. & Bourdy, R. The rostromedial tegmental nucleus gates fat overconsumption through ventral tegmental area output in male rats. Neuropsychopharmacol. (2024). https://doi.org/10.1038/s41386-024-01855-w

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