Glucagon-like peptide-1 receptor regulation of basal dopamine transporter activity is species-dependent

Jensen, Mathias E.; Galli, Aurelio; Thomsen, Morgane; Jensen, Kathrine L.; Thomsen, Gerda; Klausen, Mette K.; Vilsbøll, Tina; Christensen, Mikkel B.; Holst, Jens J.; Owens, Anthony; Robertson, Sabrina D.; Daws, Lynette C.; Zanella, Daniele; Gether, Ulrik; Knudsen, Gitte M.; Fink-Jensen, Anders

doi:10.1016/j.neuint.2020.104772

Cited by 18 publications

(15 citation statements)

References 58 publications

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“…One study focused on the lateral septum in mice, an area previously associated with reward (Harasta et al, 2015; Luo et al, 2011; Olds & Milner, 1954), and reported that GLP‐1 receptor stimulation might dampen addiction‐related effects by increasing the expression of DAT on the neuronal cell surface, thereby reducing free dopamine levels in the synapses (Reddy et al, 2016). These findings are supported by another study in rats investigating the effect of GLP‐1 receptor activation on DAT up‐regulation in striatal brain slices as well as in vivo by use of striatal microdialysis (Jensen et al, 2020). However, other studies reported unaffected DAT after exenatide treatment in rats (Fortin & Roitman, 2017), or mice (Jensen et al, 2020), or by genetic ablation of GLP‐1 receptors, that is, knockout mice (Jensen et al, 2020).…”

Section: Role Of Glp‐1 In Substance Use Disordersupporting

confidence: 54%

“…These findings are supported by another study in rats investigating the effect of GLP-1 receptor activation on DAT up-regulation in striatal brain slices as well as in vivo by use of striatal microdialysis (Jensen et al, 2020). However, other studies reported unaffected DAT after exenatide treatment in rats (Fortin & Roitman, 2017), or mice (Jensen et al, 2020), or by genetic ablation of GLP-1 receptors, that is, knockout mice (Jensen et al, 2020).…”

Section: Influence Of Glp-1 Receptor Agonists On Dopamine Regulationmentioning

confidence: 59%

“…Ten healthy volunteers with no previous history of drug or alcohol abuse received intravenous infusions of the GLP‐1 receptor agonist exenatide, while being in a SPECT scanner. The results showed no acute changes in DAT availability (Jensen et al, 2020). This is in line with findings from another clinical trial, investigating the effects of exenatide once weekly in patients with Parkinson's disease, where an effect on off‐medication motor scores was reported, but no significant effect on DAT availability after 48 weeks of treatment (Athauda et al, 2017).…”

Section: Role Of Glp‐1 In Substance Use Disordermentioning

confidence: 96%

“…This is in line with findings from another clinical trial, investigating the effects of exenatide once weekly in patients with Parkinson's disease, where an effect on off‐medication motor scores was reported, but no significant effect on DAT availability after 48 weeks of treatment (Athauda et al, 2017). Thus, it has been proposed that the GLP‐1 receptor agonist‐induced up‐regulation of DAT availability might be species dependent, with no DAT–GLP‐1 interaction in humans (Jensen et al, 2020).…”

Section: Role Of Glp‐1 In Substance Use Disordermentioning

confidence: 99%

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The role of glucagon‐like peptide 1 (GLP‐1) in addictive disorders

Klausen

Thomsen

Wörtwein

et al. 2022

British J Pharmacology

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Drug, alcohol and tobacco use disorders are a global burden affecting millions of people. Despite decades of research, treatment options are sparse or missing, and relapse rates are high. Glucagon‐like peptide 1 (GLP‐1) is released in the small intestine, promotes blood glucose homeostasis, slows gastric emptying and reduces appetite. GLP‐1 receptor agonists approved for treating Type 2 diabetes mellitus and obesity have received attention as a potential anti‐addiction treatment. Studies in rodents and non‐human primates have demonstrated a reduction in intake of alcohol and drugs of abuse, and clinical trials have been initiated to investigate whether the preclinical findings can be translated to patients. This review will give an overview of current findings and discuss the possible mechanisms of action. We suggest that effects of GLP‐1 in alcohol and substance use disorders is mediated centrally, at least partly through dopamine signalling, but precise mechanisms are still to be uncovered. LINKED ARTICLES This article is part of a themed issue on GLP1 receptor ligands (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.4/issuetoc

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Section: Role Of Glp‐1 In Substance Use Disordersupporting

confidence: 54%

Section: Influence Of Glp-1 Receptor Agonists On Dopamine Regulationmentioning

confidence: 59%

Section: Role Of Glp‐1 In Substance Use Disordermentioning

confidence: 96%

Section: Role Of Glp‐1 In Substance Use Disordermentioning

confidence: 99%

See 2 more Smart Citations

The role of glucagon‐like peptide 1 (GLP‐1) in addictive disorders

Klausen

Thomsen

Wörtwein

et al. 2022

British J Pharmacology

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“…Furthermore, the expression of GLP-1R was highest in the LS compared to all other regions, and these GLP-1 neurons were colocalized with dopamine receptor and calbindin-expressing cells in the LS (Graham et al, 2020 ). A recent study on the effect of GLP-1 on dopamine activity showed that while GLP-1 increased DA uptake, DA clearance, and DAT surface expression in the striatum in rats (Jensen et al, 2020 ). Due to its effect on ventral tegmental area (VTA) and striatal dopamine levels, it is suggested that both peripheral and central GLP-1 regulates hunger, satiety, and body weight (Kenny, 2011 ).…”

Section: Introductionmentioning

confidence: 99%

Can GLP-1 Be a Target for Reward System Related Disorders? A Qualitative Synthesis and Systematic Review Analysis of Studies on Palatable Food, Drugs of Abuse, and Alcohol

Eren-Yazicioglu

Yigit

Dogruoz

et al. 2021

Front. Behav. Neurosci.

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The role of glucagon-like peptide 1 (GLP-1) in insulin-dependent signaling is well-known; GLP-1 enhances glucose-dependent insulin secretion and lowers blood glucose in diabetes. GLP-1 receptors (GLP-1R) are also widely expressed in the brain, and in addition to its role in neuroprotection, it affects reward pathways. This systematic review aimed to analyze the studies on GLP-1 and reward pathways and its currently identified mechanisms.Methods: “Web of Science” and “Pubmed” were searched to identify relevant studies using GLP-1 as the keyword. Among the identified 26,539 studies, 30 clinical, and 71 preclinical studies were included. Data is presented by grouping rodent studies on palatable food intake, drugs of abuse, and studies on humans focusing on GLP-1 and reward systems.Results: GLP-1Rs are located in reward-related areas, and GLP-1, its agonists, and DPP-IV inhibitors are effective in decreasing palatable food intake, along with reducing cocaine, amphetamine, alcohol, and nicotine use in animals. GLP-1 modulates dopamine levels and glutamatergic neurotransmission, which results in observed behavioral changes. In humans, GLP-1 alters palatable food intake and improves activity deficits in the insula, hypothalamus, and orbitofrontal cortex (OFC). GLP-1 reduces food cravings partially by decreasing activity to the anticipation of food in the left insula of obese patients with diabetes and may inhibit overeating by increasing activity to the consumption of food in the right OFC of obese and left insula of obese with diabetes.Conclusion: Current preclinical studies support the view that GLP-1 can be a target for reward system related disorders. More translational research is needed to evaluate its efficacy on human reward system related disorders.

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