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Sex differences in response to oral amitriptyline in three animal models of depression in C57BL/6J mice

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Abstract

Rationale

Knockout and transgenic mice provide a tool for assessing the mechanisms of action of antidepressants. The effectiveness of oral administration of the tricyclic antidepressant amitriptyline (AMI) was assessed in C57BL/6J (B6) mice, a common genetic background on which knockout and transgenic mice are maintained.

Objectives

We determined whether oral AMI would have antidepressant-like effects in B6 mice and whether these effects varied according to sex, duration of treatment, and the depression model utilized.

Methods

Male and female B6 mice were administered AMI (200 μg/ml) in the drinking water as the sole source of fluid, along with 2% saccharin to increase palatability. Control mice were administered 2% saccharin alone. Mice were assessed for responsiveness to AMI in the tail suspension test (TST), the forced swim test (FST), and the learned helplessness (LH) paradigm.

Results

In the TST, AMI decreased immobility time regardless of sex or duration of treatment. AMI also decreased immobility time in the FST, but chronic treatment was necessary for full efficacy in both sexes. In the LH paradigm, both subchronic and chronic AMI treatment decreased escape latencies in female mice, but AMI was effective only after chronic treatment in males. The antidepressant-like effects of AMI could not be explained by differences in locomotor activity because activity levels were not altered by antidepressant treatment.

Conclusions

Overall, oral AMI administration provides a valid model for behavioral assessment of antidepressant-like effects in knockout and transgenic mice maintained on a B6 background, but the effectiveness of oral AMI varies depending on sex, duration of treatment, and the depression model used.

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Acknowledgements

The authors would like to thank Dr. Theresa Tritto with assistance in designing the tail suspension apparatus. This work was supported by DA00436, DA10455 and DA13334 from the National Institutes of Health and the Yale Transdisciplinary Tobacco Use Research Center.

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Authors and Affiliations

  1. Department of Psychiatry, Yale University School of Medicine, 34 Park Street, 3rd Floor Research, New Haven, CT 06508, USA

    B. J. Caldarone, K. Karthigeyan, A. Harrist, J. G. Hunsberger, E. Wittmack, S. L. King, P. Jatlow & M. R. Picciotto

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  1. B. J. Caldarone
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  2. K. Karthigeyan
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  3. A. Harrist
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  4. J. G. Hunsberger
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  6. S. L. King
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  7. P. Jatlow
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  8. M. R. Picciotto
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Correspondence to M. R. Picciotto.

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Caldarone, B.J., Karthigeyan, K., Harrist, A. et al. Sex differences in response to oral amitriptyline in three animal models of depression in C57BL/6J mice. Psychopharmacology 170, 94–101 (2003). https://doi.org/10.1007/s00213-003-1518-7

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  • DOI: https://doi.org/10.1007/s00213-003-1518-7

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