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Ghrelin’s Role in the Hypothalamic-Pituitary-Adrenal Axis Stress Response: Implications for Mood Disorders

  • Author Footnotes
    1 Authors SJS, TK, and ZBA contributed equally to this work.
    Sarah J. Spencer
    Footnotes
    1 Authors SJS, TK, and ZBA contributed equally to this work.
    Affiliations
    School of Health Sciences and Health Innovations Research Institute, RMIT University, Bundoora, Melbourne, Victoria, Australia
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  • Tim L. Emmerzaal
    Affiliations
    Department of Anatomy, Radboud University Medical Centre, Nijmegen, The Netherlands
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  • Author Footnotes
    1 Authors SJS, TK, and ZBA contributed equally to this work.
    Tamas Kozicz
    Footnotes
    1 Authors SJS, TK, and ZBA contributed equally to this work.
    Affiliations
    Department of Anatomy, Radboud University Medical Centre, Nijmegen, The Netherlands

    Hayward Genetics Center, Tulane University School of Medicine, New Orleans, Louisiana
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  • Author Footnotes
    1 Authors SJS, TK, and ZBA contributed equally to this work.
    Zane B. Andrews
    Correspondence
    Address correspondence to Zane B. Andrews, Ph.D., Monash University, Department of Physiology, School of Biomedical and Psychological Sciences, Wellington Rd, Clayton, Australia
    Footnotes
    1 Authors SJS, TK, and ZBA contributed equally to this work.
    Affiliations
    Department of Physiology, School of Biomedical and Psychological Sciences, Monash University, Clayton, Melbourne, Victoria, Australia
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  • Author Footnotes
    1 Authors SJS, TK, and ZBA contributed equally to this work.

      Abstract

      Ghrelin is a stomach hormone normally associated with feeding behavior and energy homeostasis. Recent studies highlight that ghrelin targets the brain to regulate a diverse number of functions, including learning, memory, motivation, stress responses, anxiety, and mood. In this review, we discuss recent animal and human studies showing that ghrelin regulates the hypothalamic-pituitary-adrenal axis and affects anxiety and mood disorders, such as depression and fear. We address the neural sites of action through which ghrelin regulates the hypothalamic-pituitary-adrenal axis and associated stress-induced behaviors, including the centrally projecting Edinger-Westphal nucleus, the hippocampus, amygdala, locus coeruleus, and the ventral tegmental area. Stressors modulate many behaviors associated with motivation, fear, anxiety, depression, and appetite; therefore, we assess the potential role for ghrelin as a stress feedback signal that regulates these associated behaviors. Finally, we briefly discuss important areas for future research that will help us move closer to potential ghrelin-based therapies to treat stress responses and related disorders.

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