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. Prevalence of cognitive impairment and its relation to mental health in Danish lymphoma survivors

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Effects of endogenous GIP in patients with type 2 diabetes

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Metabolic effects of 1-week binge drinking and fast food intake during Roskilde Festival in young healthy male adults

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. A high-resolution in vivo atlas of the human brain's benzodiazepine binding site of GABAA receptors

    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