Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

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

Research output: Contribution to journalJournal articleResearchpeer-review

  1. The quality of dietary carbohydrate and fat is associated with better metabolic control in persons with type 1 and type 2 diabetes

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Multidisciplinær håndtering af svær jernforgiftning som følge af suicidalforsøg

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. High-Dose Glucagon Has Hemodynamic Effects Regardless of Cardiac Beta-Adrenoceptor Blockade: A Randomized Clinical Trial

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Gut Mucosal Gene Expression and Metabolic Changes After Roux-en-Y Gastric Bypass Surgery

    Research output: Contribution to journalJournal articleResearchpeer-review

View graph of relations

INTRODUCTION: A solid body of preclinical evidence shows that glucagon-like peptide-1 receptor (GLP-1R) agonists attenuate the effects of substance use disorder related behaviors. The mechanisms underlying these effects remain elusive. In the present study, we hypothesized that GLP-1R activation modulates dopaminetransporter (DAT) and thus dopamine (DA) homeostasis in striatum. This was evaluated in three different experiments: two preclinical and one clinical.

METHODS: Rat striatal DA uptake, DA clearance and DAT cell surface expression was assessed following GLP-1 (7-36)-amide exposure in vitro. DA uptake in mice was assesed ex vivo following systemic treatment with the GLP-1R agonist exenatide. In addition, DA uptake was measured in GLP-1R knockout mice and compared with DA-uptake in wild type mice. In healthy humans, changes in DAT availability was assessed during infusion of exenatide measured by single-photon emission computed tomography imaging.

RESULTS: In rats, GLP-1 (7-36)-amide increased DA uptake, DA clearance and DAT cell surface expression in striatum. In mice, exenatide did not change striatal DA uptake. In GLP-1R knockout mice, DA uptake was similar to what was measured in wildtype mice. In humans, systemic infusion of exenatide did not result in acute changes in striatal DAT availability.

CONCLUSIONS: The GLP-1R agonist-induced modulation of striatal DAT activity in vitro in rats could not be replicated ex vivo in mice and in vivo in humans. Therefore, the underlying mechanisms of action for the GLP-1R agonists-induced efficacy in varios addiction-like behavioural models still remain.

Original languageEnglish
Article number104772
JournalNeurochemistry International
Volume138
Pages (from-to)104772
ISSN0197-0186
DOIs
Publication statusPublished - 1 Sep 2020

    Research areas

  • Addiction, Dopamine transporter, Dopamine uptake, Glucagon-like peptide-1, Striatum

ID: 60286956