Abstract
The gastrointestinal peptide glucagon-like peptide 1 (GLP-1) is known to regulate consummatory behavior and is released in response to nutrient ingestion. Analogues of this peptide recently emerged as novel pharmacotherapies for treatment of type II diabetes since they reduce gastric emptying, glucagon secretion as well as enhance glucose-dependent insulin secretion. The findings that GLP-1 targets reward related areas including mesolimbic dopamine areas indicate that the physiological role of GLP-1 extends beyond food intake and glucose homeostasis control to include reward regulation. The present series of experiments was therefore designed to investigate the effects of the GLP-1 receptor agonist, Exendin-4 (Ex4), on established nicotine-induced effects on the mesolimbic dopamine system in mice. Specifically, we show that treatment with Ex4, at a dose with no effect per se, attenuate nicotine-induced locomotor stimulation, accumbal dopamine release as well as the expression of conditioned place preference in mice. In accordance, Ex4 also blocks nicotine-induced expression of locomotor sensitization in mice. Given that development of nicotine addiction largely depends on the effects of nicotine on the mesolimbic dopamine system these findings indicate that the GLP-1 receptor may be a potential target for the development of novel treatment strategies for nicotine cessations in humans.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Conditioning, Psychological / drug effects
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Dopamine / metabolism*
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Eating / drug effects
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Exenatide
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Glucagon-Like Peptide 1 / metabolism
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Glucagon-Like Peptide-1 Receptor
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Incretins / pharmacology*
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Limbic System / drug effects*
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Limbic System / metabolism
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Male
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Mice
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Motor Activity / drug effects
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Nicotine / pharmacology
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Nucleus Accumbens / drug effects*
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Nucleus Accumbens / metabolism
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Peptides / pharmacology*
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Receptors, Glucagon / agonists*
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Receptors, Glucagon / metabolism
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Reward
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Tobacco Use Disorder / drug therapy*
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Tobacco Use Disorder / metabolism
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Tobacco Use Disorder / psychology
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Venoms / pharmacology*
Substances
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GLP1R protein, human
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Glp1r protein, mouse
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Glucagon-Like Peptide-1 Receptor
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Incretins
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Peptides
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Receptors, Glucagon
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Venoms
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Nicotine
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Glucagon-Like Peptide 1
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Exenatide
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Dopamine
Grants and funding
The research was supported by grants from the Swedish Research Council (grant no. K2006-21X-04247-33-3, 2009-2782 and K2010-80X-21496-01-6), The Swedish brain foundation, LUA/ALF (grant no. 148251) from the Sahlgrenska University Hospital, Alcohol research council of the Swedish alcohol retailing monopoly and the foundations of Adlerbertska, Fredrik and Ingrid Thuring, Tore Nilsson, Längmanska, Torsten and Ragnar Söderberg, Wilhelm and Martina Lundgren, NovoNordisk, Knut and Alice Wallenberg, Magnus Bergvall, Anérs, Jeansons, Åke Wiberg, the Swedish Society of Medicine, Swedish Society for Medical Research. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.