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Acute administration of leptin produces anxiolytic-like effects: a comparison with fluoxetine

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Abstract

Rationale

Our previous studies in rats have shown that the adipocyte-derived hormone leptin induces antidepressant-like effects with a behavioral profile similar to selective serotonin reuptake inhibitor (SSRI) antidepressants. Acute SSRI treatment causes paradoxical anxiogenic responses, although chronic treatment has therapeutic effects on anxiety. However, the role of leptin in anxiety remains to be established.

Objectives

The scope of this study was to investigate the acute effects of leptin on anxiety-related behaviors in comparison with the SSRI antidepressant fluoxetine.

Materials and methods

Adult male C57BL/6J mice received intraperitoneal injection of leptin or fluoxetine. Thirty minutes after injection, mice were subjected to the tail suspension test (TST) and forced swim test (FST) for evaluating antidepressant activity. Anxiety-like behavior was assessed in the elevated plus maze (EPM), social interaction, and open field tests 30 min following drug treatment.

Results

While leptin and fluoxetine showed similar antidepressant-like behavioral effects in the TST and FST, they differed in the behavioral assays for anxiety. Open arm exploration in the EPM was increased by leptin but decreased by fluoxetine. Analysis of social interaction revealed that distinct social behavioral components were modulated by leptin and fluoxetine. The total time of active social behaviors was increased by leptin but reduced by fluoxetine. In addition, self-grooming, a non-social behavior, was suppressed by leptin treatment. Neither leptin nor fluoxetine produced significant effects in the open field test.

Conclusions

In contrast to anxiogenic-like effects induced by acute fluoxetine, leptin elicits anxiolytic-like effects after acute administration. These results suggest that leptin has both antidepressant-like and anxiolytic-like properties.

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Acknowledgements

The authors thank Tung-Yi Huang for his contribution to this study. This work was supported by American Heart Association AHA0530345N (X.Y.L.) and National Institute of Health grants MH073844 and MH076929 (X.Y.L.).

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  1. Department of Pharmacology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX, 78229, USA

    Jing Liu, Jacob C. Garza, Jamaur Bronner, Chung Sub Kim, Wei Zhang & Xin-Yun Lu

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  1. Jing Liu
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  2. Jacob C. Garza
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Liu, J., Garza, J.C., Bronner, J. et al. Acute administration of leptin produces anxiolytic-like effects: a comparison with fluoxetine. Psychopharmacology 207, 535–545 (2010). https://doi.org/10.1007/s00213-009-1684-3

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