C/EBPβ couples dopamine signalling to substance P precursor gene expression in striatal neurones

Authors

  • Krisztián A. Kovács,

    1. Center for Psychiatric Neuroscience
    2. Service of Child and Adolescent Psychiatry, Department of Psychiatry, University Medical Center, University of Lausanne, Prilly, Switzerland
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  • Myriam Steinmann,

    1. Center for Psychiatric Neuroscience
    2. Service of Child and Adolescent Psychiatry, Department of Psychiatry, University Medical Center, University of Lausanne, Prilly, Switzerland
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  • Pierre J. Magistretti,

    1. Center for Psychiatric Neuroscience
    2. Brain and Mind Institute, Ecole Polytechnique Fédérale de Lausanne (EFPL), Lausanne, Switzerland
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  • Olivier Halfon,

    1. Service of Child and Adolescent Psychiatry, Department of Psychiatry, University Medical Center, University of Lausanne, Prilly, Switzerland
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  • Jean-René Cardinaux

    1. Center for Psychiatric Neuroscience
    2. Service of Child and Adolescent Psychiatry, Department of Psychiatry, University Medical Center, University of Lausanne, Prilly, Switzerland
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Address correspondence and reprint requests to Jean-René Cardinaux, Centre de Neurosciences Psychiatriques, 1erétage, Site de Cery, CH-1008 Prilly, Switzerland. E-mail: Jean-Rene.Cardinaux@chuv.ch

Abstract

Dopamine-induced changes in striatal gene expression are thought to play an important role in drug addiction and compulsive behaviour. In this study we report that dopamine induces the expression of the transcription factor CCAAT/Enhancer Binding Protein β (C/EBP)-β in primary cultures of striatal neurones. We identifed the preprotachykinin-A (PPT-A) gene coding for substance P and neurokinin-A as a potential target gene of C/EBPβ. We demonstrated that C/EBPβ physically interacts with an element of the PPT-A promoter, thereby facilitating substance P precursor gene transcription. The regulation of PPT-A gene by C/EBPβ could subserve many important physiological processes involving substance P, such as nociception, neurogenic inflammation and addiction. Given that substance P is known to increase dopamine signalling in the striatum and, in turn, dopamine increases substance P expression in medium spiny neurones, our results implicate C/EBPβ in a positive feedback loop, changes of which might contribute to the development of drug addiction.

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