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

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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Submitted on : Tuesday, July 16, 2019 - 4:21:45 PM
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Laure Bougarel, Jérôme Guitton, Luc Zimmer, Jean-Marie Vaugeois, Malika El Yacoubi. Behaviour of a genetic mouse model of depression in the learned helplessness paradigm. Psychopharmacology, 2011, 215 (3), pp.595-605. ⟨10.1007/s00213-011-2218-3⟩. ⟨hal-02185484⟩



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