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Gut-brain Axis: Involvement of gastrointestinal hormones in addictive disorders

Addictive disorders are one of the most serious public health problems and constitute a considerable cost to society. The neurochemical mechanisms involved are complex and we were the first to show that the hunger-regulatory hormones ghrelin, glucagon-like peptide-1 (GLP-1) and neuromedin U (NMU) may function as players of the reward scene and thus be important for development of addiction. The involvement of this gut-brain axis is now investigated further. Our recent data show that GLP-1 regulates alcohol-mediated behaviors as well as reward induced by other addictive drugs in rodents. In addition, preliminary data show that central administration of NMU reduces alcohol intake in rats. Other parameters, such as motivation, craving and relapse, are equally important parts of addiction. We will therefore examine the role of GLP-1 and NMU receptors in reward-related areas for these parameters. The possibility that NMU can mediate reward, including release of accumbal dopamine, induced by addictive drugs will be studied in mice. Planned experiments will also elucidate the role of ghrelin, GLP-1 and NMU for other addictive disorders mandated via the reward systems. Therefore, the ability of these gut-brain peptides to influence sexual motivation and interaction in male mice as well as for the motivation to consume sucrose in rats will be investigated. We will examine the associations between GLP-1 as well as NMU related genes and high alcohol intake in human genetic studies. In a clinical study the effects of GLP-1 analogues on alcohol intake in patients with AUD will be investigated. Collectively this adds to a translational strategy where human genetic studies and clinical study in humans strengthen our preclinical data. With the knowledge obtained by the present project proposal novel treatment strategies for addictive disorders may be developed.

Elisabet Jerlhag Holm

Associate Professor, Project Leader
Phone: 786 34 18
Email: elisabet.jerlhag@pharm.gu.se

Research group members

Petra Suchankova Karlsson; Postdoctoral Fellow, PhD

Caroline Wass; Postdoctoral Fellow, PhD, Associate Professor

Daniel Vallöf; PhD student

Aimilia Lydia Kalafateli; PhD student

Jesper Vestlund; PhD student

Britt-Mari Larsson; Laboratory technician

Jörgen Engel; Senior Professor, MD, PhD
 

Page Manager: Lennart Svensson|Last update: 4/5/2017
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