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Acute tianeptine treatment selectively modulates neuronal activation in the central nucleus of the amygdala and attenuates fear extinction

Molecular Psychiatry volume 20, pages 1420–1427 (2015)Cite this article

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Abstract

Antidepressant drugs are commonly prescribed treatments for anxiety disorders, and there is growing interest in understanding how these drugs impact fear extinction because extinction learning is pivotal to successful exposure-based therapy (EBT). A key objective within this domain is understanding how antidepressants alter the activation of specific elements of the limbic-based network that governs such fear processing. Chronic treatment with the antidepressant tianeptine has been shown to reduce the acquisition of extinction learning in rats, yet the drug’s acute influence on activation in prefrontal and amygdalar regions, and on extinction learning are not well understood. To assess its influence on cellular activation, rats were injected with tianeptine and Fos immunoreactivity was measured in these regions. Acute tianeptine treatment selectively altered Fos expression within subdivisions of the central nucleus of the amygdala (CEA) in a bidirectional manner that varied in relation to ongoing activation within the capsular subdivision and its prefrontal and intra-amygdalar inputs. This pattern of results suggests that the drug can conditionally modulate the activation of CEA subdivisions, which contain microcircuits strongly implicated in fear processing. The effect of acute tianeptine was also examined with respect to the acquisition, consolidation and expression of fear extinction in rats. Acute tianeptine attenuated extinction learning as well as the recall of extinction memory, which underscores that acute dosing with the drug could alter learning during EBT. Together these findings provide a new perspective for understanding the mechanism supporting tianeptine’s clinical efficacy, as well as its potential influence on CEA-based learning mechanisms.

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Acknowledgements

We thank MJ Sanders and CK Cain for their comments on the manuscript, and A Hambucken, E Davenas and A Eckmier for their technical assistance. BP Godsil was supported by fellowships from INSERM as well as financial support from IRS, Servier Company. B Bontempi was supported by funding from the Fondation pour la Recherche Médicale (FRM: DEQ20130326468), CNRS and University of Bordeaux. This work was partially funded by grants from INSERM and IRS.

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Authors and Affiliations

  1. Institut National de la Santé et de la Recherche Médicale (INSERM) UMR_S894, Laboratoire de Physiopathologie des Maladies Psychiatriques, Centre de Psychiatrie et Neurosciences, Paris, France

    B P Godsil, F Mailliet & T M Jay

  2. Université Paris Descartes, Paris, France

    B P Godsil, F Mailliet & T M Jay

  3. Institut des Maladies Neurodégénératives, Université de Bordeaux, UMR 5293, Bordeaux, France

    B Bontempi

  4. ICNRS, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France

    B Bontempi

  5. Institut de Recherche, Servier (IRS), Suresnes, France

    P Delagrange & M Spedding

  6. Spedding Research Solutions, Le Vesinet, France

    M Spedding

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  1. B P Godsil
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Correspondence to B P Godsil.

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The authors declare that the research of BP Godsil, including salary, has been supported by grants from INSERM and IRS. TM Jay is employed by INSERM, and her research has been supported by grants from INSERM and IRS. M Spedding was employed by IRS and Les Labotaoires Servier. P Delegrange is currently employed by IRS and Les Labotaoires Servier. The remaining authors declare no conflict of interest.

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Godsil, B., Bontempi, B., Mailliet, F. et al. Acute tianeptine treatment selectively modulates neuronal activation in the central nucleus of the amygdala and attenuates fear extinction. Mol Psychiatry 20, 1420–1427 (2015). https://doi.org/10.1038/mp.2014.169

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