Depleting adult dentate gyrus neurogenesis increases cocaine-seeking behavior

Abstract

The hippocampus is the main locus for adult dentate gyrus (DG) neurogenesis. A number of studies have shown that aberrant DG neurogenesis correlates with many neuropsychiatric disorders, including drug addiction. Although clear causal relationships have been established between DG neurogenesis and memory dysfunction or mood-related disorders, evidence of the causal role of DG neurogenesis in drug-seeking behaviors has not been established. Here we assessed the role of new DG neurons in cocaine self-administration using an inducible transgenic approach that selectively depletes adult DG neurogenesis. Our results show that transgenic mice with decreased adult DG neurogenesis exhibit increased motivation to self-administer cocaine and a higher seeking response to cocaine-related cues. These results identify adult hippocampal neurogenesis as a key factor in vulnerability to cocaine addiction.

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Acknowledgements

This work was financially supported by INSERM, Agence Nationale pour la Recherche (to DNA: ANR n°06-NEURO-00 2-01), Aquitaine Regional Council and University of Bordeaux. This work benefited from the support of the Animal Housing and Genotyping facilities. The technical helps of Mr C Dupuy and Mrs V Roullot-Lacarrière, are gratefully acknowledged.

Author contributions:

Conception and design of experiments: PVP, DNA, VDG, JMR. Performed the experiments: JFF, EB, MK, NG, JMR. Acquisition of the data, analysis and interpretation of the data: VDG, JMR, MK, DNA, PVP. Wrote the paper: VDG, JMR, MK, DNA, PVP.

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The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

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Correspondence to Djoher Nora Abrous.

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These authors contributed equally: Véronique Deroche-Gamonet, Jean-Michel Revest, Djoher Nora Abrous, Pier-Vincenzo Piazza.

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Deroche-Gamonet, V., Revest, J., Fiancette, J. et al. Depleting adult dentate gyrus neurogenesis increases cocaine-seeking behavior. Mol Psychiatry 24, 312–320 (2019). https://doi.org/10.1038/s41380-018-0038-0

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