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Chronic social defeat stress model: behavioral features, antidepressant action, and interaction with biological risk factors

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Abstract

Rationale

Chronic social defeat stress (CSDS) has been proposed as a model of depression. However, most CSDS studies rely only on the analysis of stress-induced social avoidance. Moreover, the predictive validity of the model has been poorly analyzed, let alone its interaction with biological risk factors.

Objectives

Here, we explore the validity of CSDS as a depression model. Further, the effect of decreased vesicular glutamate transporter 1 (VGLUT1), as a potential factor enhancing a depressive-like phenotype, was studied.

Methods

Mice were exposed to CSDS (10 days) followed by saline, venlafaxine, fluoxetine, or tianeptine treatment (30 days). The battery of behaviors included motor activity, memory, anxiety, social interaction, helplessness, and anhedonic-like behavior. Moreover, the behavioral effect of CSDS in VGLUT1 heterozygous (VGLUT1+/−) mice was studied, as well as the regulation of VGLUT1 mRNA.

Results

CSDS induced anhedonia, helplessness, hyperactivity, anxiety, social avoidance, and freezing, as well as downregulation of VGLUT1 mRNA in the amygdala. Repeated venlafaxine showed antidepressant-like activity and both venlafaxine and tianeptine behaved as effective anxiolytics. CSDS-induced social avoidance was reverted by tianeptine. Fluoxetine failed to revert most of the behavioral alterations. VGLUT1+/− mice showed an enhanced vulnerability to stress-induced social avoidance.

Conclusion

We suggest that CSDS is not a pure model of depression. Indeed, it addresses relevant aspects of anxiety-related disorders. Firstly, CSDS-induced anhedonia and social avoidance are not associated in this model. Moreover, CSDS might be affecting brain areas mainly involved in the processing of social behavior, such as the amygdala, where the glutamatergic mechanism could play a key role.

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Acknowledgments

We are very grateful to Ms. Sandra Lizaso and M.L. Muro for their excellent technical assistance. We are also very grateful to Dr. S. Wojcik (Gottingen, Germany) for the generous gift of the VGLUT1+/− mice. This work was supported by Laboratories Servier S.L., the Ministry of Science and Innovation (SAF2008-02217, Spanish Government), and a fellowship from the Spanish Government (Department of Education) to N. Elizalde.

Conflict of interest

All the authors report no biomedical financial interests or potential conflicts of interest.

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Authors and Affiliations

  1. Department of Pharmacology, University of Navarra, 31080, Pamplona, Spain

    E. Venzala, A. L. García-García, N. Elizalde & R. M. Tordera

  2. Department of Psychiatry, Division of Integrative Neuroscience, Columbia University, New York, USA

    A. L. García-García

  3. Institut de Recherches Servier, Suresnes, France

    P. Delagrange

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  1. E. Venzala
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  2. A. L. García-García
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  3. N. Elizalde
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Correspondence to R. M. Tordera.

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Fig. 1S

Effect of social defeat stress in VGLUT1+/− and WT littermates on the weight gain (a), motor activity (b) and anxiety-like behavior in the elevated plus maze test (c) and in the novelty suppression of feeding test (e). Data show mean ± SEM (n = 18 mice/group) of the weight gain from the day 1 of the CSDS procedure (a) and mean ± SEM of the distance traveled during 30 min (b). In the measurement of anxiety behavior, data show mean ± SEM (n = 18 mice/group) of the time spent in open arms (c) in the elevated plus maze test. In the novelty suppression of feeding test, data show mean ± SEM of the time spent in the eating zone (d) (*p < 0.05, ** p < 0.01 vs. WT) (JPEG 138 kb)

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Venzala, E., García-García, A.L., Elizalde, N. et al. Chronic social defeat stress model: behavioral features, antidepressant action, and interaction with biological risk factors. Psychopharmacology 224, 313–325 (2012). https://doi.org/10.1007/s00213-012-2754-5

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