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The orexigenic hormone ghrelin defends against depressive symptoms of chronic stress


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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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



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.

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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).

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