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Loss of dopaminergic nigrostriatal neurons accounts for the motivational and affective deficits in Parkinson’s disease

Molecular Psychiatry volume 19, pages 358–367 (2014)Cite this article

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Abstract

Parkinson’s disease (PD) involves the degeneration of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc) that is thought to cause the classical motor symptoms of this disease. However, motivational and affective impairments are also often observed in PD patients. These are usually attributed to a psychological reaction to the general motor impairment and to a loss of some of the neurons within the ventral tegmental area (VTA). We induced selective lesions of the VTA and SNc DA neurons that did not provoke motor deficits, and showed that bilateral dopamine loss within the SNc, but not within the VTA, induces motivational deficits and affective impairments that mimicked the symptoms of PD patients. Thus, motivational and affective deficits are a core impairment of PD, as they stem from the loss of the major group of neurons that degenerates in this disease (DA SNc neurons) and are independent of motor deficits.

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Acknowledgements

This work was supported by the Institut National de la Santé et de la Recherche Médicale, Fondation NeuroDis, Association France Parkinson, Ministère de la Recherche et de la technologie (MRT), Région Rhône-Alpes (ARC n°2) and Université Joseph Fourier. We would also like to thank Maurice Demattéis and Paul Krack for helpful discussions.

Author contributions

GD, SC and MS were responsible for overall study design. GD, SC, MF and SB carried out the stereotaxic surgeries and the post-surgery monitoring of the animals. CC, GD and SC carried out the neuroanatomical analysis and characterization of the lesions. SC and GD performed the experiment for the neurochemical characterization of the lesion. AB carried out the HPLC process and analysis. SC and GD carried out the behavioral experiments and analysis. GD, SC and MS wrote the paper with the help of the other authors.

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Author notes

  1. G Drui and S Carnicella: These authors contributed equally to this work.

Authors and Affiliations

  1. Institut National de la Santé et de la Recherche Médicale, Unité 836, Grenoble Institut des Neurosciences, Dynamique et Physiopathologie des Ganglions de la Base, Grenoble, France

    G Drui, S Carnicella, C Carcenac, M Favier, A Bertrand, S Boulet & M Savasta

  2. Université Joseph Fourier, Grenoble, France

    G Drui, S Carnicella, C Carcenac, M Favier, A Bertrand, S Boulet & M Savasta

  3. Centre Hospitalier Universitaire de Grenoble, Grenoble, France

    M Savasta

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  1. G Drui
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Correspondence to M Savasta.

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Drui, G., Carnicella, S., Carcenac, C. et al. Loss of dopaminergic nigrostriatal neurons accounts for the motivational and affective deficits in Parkinson’s disease. Mol Psychiatry 19, 358–367 (2014). https://doi.org/10.1038/mp.2013.3

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