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Ghrelin Antagonism: A Potential Therapeutic Target for Addictive Behaviour Disorders

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Ghrelin in Health and Disease

Part of the book series: Contemporary Endocrinology ((COE,volume 10))

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Abstract

Here we review the emerging evidence for a role of the central ghrelin signalling system in reward from food (i.e. a natural reward) as well as from alcohol and other drugs of abuse (i.e. artificial rewards). Ghrelin levels are high preprandially consistent with a role in hunger and meal initiation. The hypothalamic and brainstem circuits involved in energy balance are clearly important targets for ghrelin. However, ghrelin also activates a key reward circuit, the cholinergic-dopaminergic reward link, that is involved in motivated reward-driven behaviour. This reward link comprises a dopamine projection from the ventral tegmental area (VTA) to the nucleus accumbens together with a cholinergic input, arising primarily from the laterodorsal tegmental area. Direct injection of ghrelin into the brain ventricles or into the VTA increases the consumption of rewarding foods as well as alcohol in mice and rats. Conversely, ghrelin receptor (GHS-R1A) antagonists suppress reward from chemical drugs and also from rewarding foods, thereby decreasing their consumption. Variations in the GHS-R1A and pro-ghrelin genes have been associated with high alcohol consumption, smoking and increased body mass index in alcohol-dependent individuals as well as with bulimia nervosa and obesity. Thus, the central ghrelin signalling system is strongly implicated in reward from food as well as chemical drugs, thereby providing a potential therapeutic target for addictive behaviour disorders, including those associated with compulsive overeating, obesity as well as substance use disorder.

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Acknowledgments

The research was supported by the EU (FP7-HEALTH-2009–241592, FP7-KBBE-2009-3-245009), Swedish Medical Research Council (K2007-54X-20328–013, K2006-21X-04247-33-3), ALF/LUA grants from the Sahlgrenska Hospital Göteborg (SU7601, 7136, 7341), the Alcohol Research Council of the Swedish Alcohol Retailing Monopoly, The Swedish brain foundation, the foundations of Wilhelm and Martina Lundgren, Knut and Alice Wallenberg, The Adlerbert Research, Thuring’s, Längmanska art, Torsten and Ragnar Söderberg, Magnus Bergvall foundation, The Swedish Society of Medicine and the Swedish Foundation for Strategic Research to Sahlgrenska Center for Cardiovascular and Metabolic Research (A305-188). Thanks to Dr. Anders Friberg for help in preparing figures and for proofreading the text.

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Authors and Affiliations

  1. Department of Pharmacology, University of Gothenburg, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, Gothenburg, Sweden

    Elisabet Jerlhag Ph.D. & Jörgen Engel Ph.D., M.D.

  2. Department of Physiology, University of Gothenburg, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, Gothenburg, Sweden

    Emil Egecioglu Ph.D., M.Sc.

  3. The Sahlgrenska Academy at the University of Gothenburg, Institute of Neuroscience and Physiology, Medicinaregatan 11, Gothenburg, 436 44, Sweden

    Suzanne L. Dickson B.Sc., Ph.D.

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  1. Elisabet Jerlhag Ph.D.
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Correspondence to Suzanne L. Dickson B.Sc., Ph.D. .

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  1. , Department of Metabolism and Aging, The Scripps Research Institute Florida, Scripps Way 3B3 130, Jupiter, 33458, Florida, USA

    Roy G. Smith

  2. , Department of Medicine, University of Virginia, Ray C Hunt Drive 450, Charlottesville, 22908, Virginia, USA

    Michael O. Thorner

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Jerlhag, E., Egecioglu, E., Engel, J., Dickson, S.L. (2012). Ghrelin Antagonism: A Potential Therapeutic Target for Addictive Behaviour Disorders. In: Smith, R., Thorner, M. (eds) Ghrelin in Health and Disease. Contemporary Endocrinology, vol 10. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-61779-903-7_10

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