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GLP-1 signaling and alcohol-mediated behaviors; preclinical and clinical evidence.

Forskningsöversiktsartikel
Författare Elisabeth Jerlhag
Publicerad i Neuropharmacology
Volym 136
Nummer/häfte Special issue
Sidor 343-349
ISSN 1873-7064
Publiceringsår 2018
Publicerad vid Institutionen för neurovetenskap och fysiologi, sektionen för farmakologi
Sidor 343-349
Språk en
Länkar dx.doi.org/10.1016/j.neuropharm.201...
www.ncbi.nlm.nih.gov/entrez/query.f...
Ämnesord Dopamine; Gut-brain axis; Incentive salience; Motivation; Reinforcement
Ämneskategorier Neurovetenskap

Sammanfattning

Alcohol addiction, affecting approximately four percent of the population, contributes significantly to the global burden of diseases and is a substantial cost to the society. The neurochemical mechanisms regulating alcohol mediated behaviors is complex and in more recent years a new physiological role of the gut-brain peptides, traditionally known to regulate appetite and food intake, have been suggested. Indeed, regulators of alcohol-mediated behaviors. One of these gut-brain peptides is the annorexigenic peptide glucagon-like peptide-1 (GLP-1), Preclinical studies show that GLP-1 receptor activation, either by GLP-1 or analogues, attenuate the ability of alcohol to activate the mesolimbic dopamine system as well as decrease alcohol consumption and operant self-administration. In further support for the endogenous GLP-1 system in addiction processes are the experimental data showing that a GLP-1 receptor antagonist increases alcohol intake. Moreover, GLP-1 receptor agonists prevent the ability of other addictive drugs to activate the mesolimbic dopamine system. The number of clinical studies is limited, but show i) that genetic variation in the GLP-1 receptor gene is associated with alcohol addiction as well as increased alcohol infusion in humans, ii) that plasma levels of GLP-1 are associated with the subjective experience of cocaine and iii) that a GLP-1 receptor agonist reduces alcohol intake in patients with type-2 diabetes mellitus. These experimental and clinical studies raises the concern that clinically available GLP-1 receptor agonists deserves to be tested as potential treatments of patients with addictive disorders including alcohol addiction.

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