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The orexigenic hormone ghrelin defends against depressive symptoms of chronic stress

Nature Neuroscience volume 11, pages 752–753 (2008)Cite this article

Abstract

We found that increasing ghrelin levels, through subcutaneous injections or calorie restriction, produced anxiolytic- and antidepressant-like responses in the elevated plus maze and forced swim test. Moreover, chronic social defeat stress, a rodent model of depression, persistently increased ghrelin levels, whereas growth hormone secretagogue receptor (Ghsr) null mice showed increased deleterious effects of chronic defeat. Together, these findings demonstrate a previously unknown function for ghrelin in defending against depressive-like symptoms of chronic stress.

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Figure 1: Anxiolytic- and antidepressant-like effects of ghrelin signaling.
Figure 2: Ghrelin signaling regulates social isolation after CSDS.

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Acknowledgements

The authors thank C.E. Lee, M. Choi and M. Perello. This work was supported by grants from the US National Institutes of Health (K08DK068069-01A2, R01DK71320, P01DK56116, RL1DK081185, P50MH66172 and ADA 1-06-JF-59), a Foundation for Prader-Willi Research Grant, an NARSAD Young Investigator Award and a University of Texas Southwestern Disease-Oriented Clinical Scholars Award. M.Y. is a Howard Hughes Medical Institute investigator.

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Authors and Affiliations

  1. Department of Psychiatry, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, 75390-9077, Texas, USA

    Michael Lutter, Saendy Jung, Shari Birnbaum, Joel K Elmquist & Eric J Nestler

  2. Department of Internal Medicine (Divisions of Hypothalamic Research and Endocrinology and Metabolism), The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, 75390-9077, Texas, USA

    Ichiro Sakata, Sherri Osborne-Lawrence, Sherry A Rovinsky, Jason G Anderson, Joel K Elmquist & Jeffrey M Zigman

  3. Department of Molecular Genetics and Howard Hughes Medical Institute, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, 75390-9077, Texas, USA

    Masashi Yanagisawa

  4. Department of Pharmacology, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, 75390-9077, Texas, USA

    Joel K Elmquist

Authors
  1. Michael Lutter
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  2. Ichiro Sakata
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  9. Joel K Elmquist
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  10. Eric J Nestler
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  11. Jeffrey M Zigman
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Contributions

M.L. and J.M.Z. conceived, designed and performed these studies, analyzed the data and wrote the manuscript. I.S. assisted on all pharmacologic experiments. S.O.-L., S.A.R. and J.G.A. maintained the mouse colony and genotyped the mice. S.B. and S.J. assisted with the behavioral testing. M.Y. provided the orexin-deficient mice. J.K.E. and E.J.N. helped supervise and fund these studies, and critiqued the manuscript.

Corresponding author

Correspondence to Jeffrey M Zigman.

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Supplementary Figures 1–4 and Supplementary Methods (PDF 160 kb)

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Lutter, M., Sakata, I., Osborne-Lawrence, S. et al. The orexigenic hormone ghrelin defends against depressive symptoms of chronic stress. Nat Neurosci 11, 752–753 (2008). https://doi.org/10.1038/nn.2139

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