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Behaviour of a genetic mouse model of depression in the learned helplessness paradigm

Psychopharmacology volume 215, pages 595–605 (2011)Cite this article

Abstract

Rationale

H/Rouen (displaying a helpless phenotype in the tail suspension test) mice exhibiting features of depressive disorders and NH/Rouen (displaying non-helpless phenotype) mice were previously created through behavioural screening and selective breeding. Learned helplessness (LH), in which footshock stress induces a coping deficit, models some aspects of depression in rodents, but so far, fewer LH studies have been performed in mice than in rats.

Objectives

To study H/Rouen and NH/Rouen in the LH paradigm.

Results

When CD1 mice were submitted to footshock with various training durations and shock intensities, the most suitable parameters to induce a behavioural deficit were 0.3 mA and four training sessions. A significantly longer latency to escape shocks was found in male H/Rouen mice compared to male NH/Rouen mice. On the other hand, once shocked, NH/Rouen mice showed more severe coping deficits than H/Rouen mice. In addition, a sub-chronic treatment with fluoxetine lacked efficacy in NH/Rouen mice, whereas it improved performances in H/Rouen mice. We also found that a shock reminder at day 8, subsequent to inescapable shocks, maintained helplessness for 20 days. Finally, female H/Rouen mice responded to chronic fluoxetine administration after 10 days of treatment, while a 20-day treatment was necessary to improve the behavioural deficit in H/Rouen male mice.

Conclusion

H/Rouen and NH/Rouen lines displayed different despair-related behaviour in the LH paradigm. Fluoxetine had beneficial effects after sub-chronic or chronic but not acute treatment of H/Rouen mice, thus providing a pharmacological validation of the protocols.

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Affiliations

  1. Centre de Recherche en Neurosciences de Lyon, CNRS UMR 5292/INSERM U1028 Physiopathologie des réseaux neuronaux du cycle veille-sommeil, Faculté de Pharmacie, Université Lyon 1, 8 avenue Rockefeller, 69373, Lyon Cedex 08, France

    Laure Bougarel, Jean-Marie Vaugeois & Malika El Yacoubi

  2. Département de pharmacologie, Université de Rouen, U.F.R. Médecine & Pharmacie, 76183, Rouen Cedex 1, France

    Jean-Marie Vaugeois

  3. Centre de Recherche en Neurosciences de Lyon CNRS UMR5292/INSERM U1028, Biomarqueurs radiopharmaceutiques et neurochimiques, CERMEP-Hospices Civils de Lyon, 59 bd Pinel, 69003, Lyon, France

    Luc Zimmer

  4. Département de Physiologie, Pharmacologie et Toxicologie, Faculté de Pharmacie, Université Lyon 1, 8 avenue Rockefeller, 69373, Lyon Cedex 08, France

    Jérôme Guitton, Luc Zimmer & Jean-Marie Vaugeois

Authors
  1. Laure Bougarel
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  2. Jérôme Guitton
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  3. Luc Zimmer
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  4. Jean-Marie Vaugeois
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  5. Malika El Yacoubi
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Correspondence to Malika El Yacoubi.

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Bougarel, L., Guitton, J., Zimmer, L. et al. Behaviour of a genetic mouse model of depression in the learned helplessness paradigm. Psychopharmacology 215, 595–605 (2011). https://doi.org/10.1007/s00213-011-2218-3

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  • DOI: https://doi.org/10.1007/s00213-011-2218-3

Keywords

  • Learned helplessness
  • Fluoxetine
  • Mouse model of depression
  • Tail suspension test
  • Selective breeding