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Stress and addiction: glucocorticoid receptor in dopaminoceptive neurons facilitates cocaine seeking

Nature Neuroscience volume 12, pages 247–249 (2009)Cite this article

Abstract

The glucocorticoid receptor is a ubiquitous transcription factor mediating adaptation to environmental challenges and stress. Selective Nr3c1 (the glucocorticoid receptor gene) ablation in mouse dopaminoceptive neurons expressing dopamine receptor 1a, but not in dopamine-releasing neurons, markedly decreased the motivation of mice to self-administer cocaine, dopamine cell firing and the control exerted by dopaminoceptive neurons on dopamine cell firing activity. In contrast, anxiety was unaffected, indicating that glucocorticoid receptors modify a number of behavioral disorders through different neuronal populations.

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Figure 1: Glucocorticoid receptor inactivation in the dopamine neurons of GRDATcre sup>Slc6-cre mice and in the dopaminoceptive neurons of GRD1aCre mice.
Figure 2: Glucocorticoid receptor inactivation in dopamine receptor 1a–expressing neurons, but not in dopamine-releasing neurons, reduces the motivational properties of cocaine.
Figure 3: Glucocorticoid receptor in dopaminoceptive, but not in dopamine neurons, controls the firing rates and patterns of VTA dopamine neurons.

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Acknowledgements

We thank C. Kellendonk, J.P. Tassin, S. Vyas, M. Koehl and O. George for discussions, and J.D. Rouzeau and H. Cambier for excellent technical assistance. This work was supported by grants from Action Concertée Incitative Neurosciences, Agence Nationale de la Recherche (Neuro-GRADA) and European Union Sixth Framework Programme (STREP-PheCOMP ) to F.T. and P.V.P., Centre National de la Recherche ATIPE, Fondation pour la Recherche Médicale, Mission Interministérielle de Lutte contre la Drogue et la Toxicomanie, NRJ-Foundation and European Union Sixth Framework Programme (STREP-NovelTune) to F.T., and Deutsche Forschungsgemeinschaft (SFB636) to G.S. Mission Interministérielle de Lutte contre la Drogue et la Toxicomanie and Fondation pour la Recherche Médicale supported M.T.

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Author notes

  1. Frédéric Ambroggi & Michela Marinelli

    Present address: Current addresses: Ernest Gallo Clinic and Research Center, Department of Neurology, University of California, San Francisco, 5858 Horton Street, Suite 200, Emeryville, California 94608, USA (F.A.), Department of Cellular and Molecular Pharmacology, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois 60064, USA (M.M.).,

  2. Frédéric Ambroggi, Marc Turiault, Pier Vincenzo Piazza and François Tronche: These authors contributed equally to this work.

Authors and Affiliations

  1. INSERM U862, NeuroCenter Magendie, Pathophysiology of Addiction, 147 Rue Léo Saignat, Bordeaux, 33077, Cedex, France

    Frédéric Ambroggi, Véronique Deroche-Gamonet, Eric Balado, Rixt van der Veen, Michela Marinelli & Pier Vincenzo Piazza

  2. Université de Bordeaux, Pathophysiology of Addiction, 147 Rue Léo Saignat, Bordeaux, 33077, Cedex, France

    Frédéric Ambroggi, Véronique Deroche-Gamonet, Eric Balado, Rixt van der Veen, Michela Marinelli & Pier Vincenzo Piazza

  3. CNRS UMR7148, Molecular Genetics, Neurophysiology and Behavior, 11 place Marcelin Berthelot, Paris, 75231, Cedex 5, France

    Marc Turiault, Aude Milet, Sébastien Parnaudeau, Jacques Barik, Grégoire Maroteaux, Monique Lazar & François Tronche

  4. Collège de France, Institut de Biologie, Molecular Genetics, Neurophysiology and Behavior, 11 place Marcelin Berthelot, Paris, 75231, Cedex 5, France

    Marc Turiault, Aude Milet, Sébastien Parnaudeau, Jacques Barik, Grégoire Maroteaux, Monique Lazar & François Tronche

  5. CNRS UMR7224 Campus Jussieu, 9 quai Saint Bernard, Paris, 75252, Cedex 05, France

    Sébastien Parnaudeau, Jacques Barik & François Tronche

  6. Molecular Biology of the Cell I, German Cancer Research Center, Im Neuenheimer Feld 280, Heidelberg, 69120, Germany

    Thomas Lemberger & Günther Schütz

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  1. Frédéric Ambroggi
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Contributions

M.T. and S.P. generated the mice. M.T. performed the self-administration experiments with help from F.A. and E.B. A.M., J.B., S.P., R.v.d.V. and G.M. carried out the behavioral experiments and hormone dosages, and F.A. and M.M. performed the electrophysiology experiments. V.D.-G., M.L. and M.M. were involved in study design. T.L. and G.S. provided the Drd1a-cre transgenic mouse line. P.V.P. and F.T. designed the study and obtained funding.

Corresponding authors

Correspondence to Pier Vincenzo Piazza or François Tronche.

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Ambroggi, F., Turiault, M., Milet, A. et al. Stress and addiction: glucocorticoid receptor in dopaminoceptive neurons facilitates cocaine seeking. Nat Neurosci 12, 247–249 (2009). https://doi.org/10.1038/nn.2282

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