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Antidepressant response to chronic citalopram treatment in eight inbred mouse strains

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Abstract

Rationale

The antidepressant response exhibits a characteristic delay. BALB/cJ mice respond to chronic, but not subchronic, treatment with selective serotonin reuptake inhibitors (SSRIs), providing a model of antidepressant onset. Identification of other mouse strains exhibiting this phenotype will provide additional tools for studying mechanisms of the antidepressant response.

Objectives

We aimed to identify inbred mouse strains that respond to chronic, but not subchronic, SSRI treatment in the forced swim test (FST). We also assessed whether response correlated with genotype at the functional C1473G polymorphism in tryptophan hydroxylase-2 (Tph2).

Methods

BALB/cJ, three closely related strains (BALB/cByJ, SEA/GnJ, A/J), and four distantly related strains (C57BL/6J, C57BL/10J, CAST/EiJ, SM/J) received the SSRI citalopram (0–30 mg/kg/day in drinking water) for ~4 weeks and were assessed for locomotion and FST behavior. Citalopram-responsive strains were assessed identically following ~1 week of treatment. C1473G genotypes were determined.

Results

BALB/cJ and related strains carried the 1473G allele and responded to chronic citalopram treatment in the FST. BALB/cJ, BALB/cByJ, and SEA/GnJ mice showed either no response or an attenuated response to subchronic treatment. Distantly related strains carried the 1473C allele and showed no response to citalopram. No relationship was found between the antidepressant response and baseline immobility or locomotion.

Conclusions

BALB/cJ and related strains exhibit an antidepressant response to chronic SSRI treatment that emerges over time and is likely a heritable trait. This antidepressant response is associated with carrying the 1473G allele in Tph2. In conclusion, BALB/cJ and related strains provide valuable models for studying the therapeutic mechanisms of SSRIs.

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Acknowledgments

This work was supported by National Institutes of Health grants K01MH071555 and R01MH079424 to S.C.D.

Conflict of interest

None of the authors reported biomedical financial interests or potential conflicts of interest.

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Authors and Affiliations

  1. Committee on Neurobiology, University of Chicago, Chicago, IL, 60637, USA

    Stephanie C. Dulawa

  2. Department of Psychiatry, University of Chicago, 924 East 57th Street, Room R018, MC 3077, Chicago, IL, 60637, USA

    Jianwei Jiao, Angela M. Nitzke, Demetrios G. Doukas, Mariel P. Seiglie & Stephanie C. Dulawa

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  1. Jianwei Jiao
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  2. Angela M. Nitzke
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  3. Demetrios G. Doukas
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  4. Mariel P. Seiglie
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  5. Stephanie C. Dulawa
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Corresponding author

Correspondence to Stephanie C. Dulawa.

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Jiao, J., Nitzke, A.M., Doukas, D.G. et al. Antidepressant response to chronic citalopram treatment in eight inbred mouse strains. Psychopharmacology 213, 509–520 (2011). https://doi.org/10.1007/s00213-010-2140-0

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  • DOI: https://doi.org/10.1007/s00213-010-2140-0

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