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GLP-1 receptor agonists have a sustained stimulatory effect on corticosterone release after chronic treatment

Published online by Cambridge University Press:  03 December 2014

Maarja Krass ,
Annika Volke ,
Kertu Rünkorg ,
Gregers Wegener ,
Sten Lund ,
Anders Abildgaard Open the ORCID record for Anders Abildgaard [Opens in a new window] ,
Eero Vasar  and
Vallo Volke
Maarja Krass
Affiliation:
Department of Physiology, University of Tartu, Tartu, Estonia Center for Translational Medicine, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia
Annika Volke
Affiliation:
Department of Dermatology; University of Tartu, Tartu, Estonia
Kertu Rünkorg
Affiliation:
Department of Physiology, University of Tartu, Tartu, Estonia Center for Translational Medicine, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia
Gregers Wegener
Affiliation:
Translational Neuropsychiatry Unit, Aarhus University, Risskov, Denmark Centre of Excellence for Pharmaceutical Sciences, School of Pharmacy (Pharmacology), North-West University, Potchefstroom, South Africa
Sten Lund
Affiliation:
Medical Department MEA (Endocrinology), Aarhus University Hospital, Aarhus C, Denmark
Anders Abildgaard
Affiliation:
Translational Neuropsychiatry Unit, Aarhus University, Risskov, Denmark
Eero Vasar
Affiliation:
Department of Physiology, University of Tartu, Tartu, Estonia Center for Translational Medicine, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia
Vallo Volke*
Affiliation:
Department of Physiology, University of Tartu, Tartu, Estonia Center for Translational Medicine, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia
*
Prof. Vallo Volke, Department of Physiology, Institute of Biomedicine and Translational Medicine University of Tartu, 19 Ravila Street, 50411 Tartu, Estonia. Tel. +372 7 374338; Fax: +372 7 374332;E-mail: vallo.volke@ut.ee
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Abstract

Objective

Glucagon-like peptide 1 (GLP-1) receptor agonists are a new group of antidiabetic medications quickly gaining popularity. We aimed to examine behavioural and neuroendocrine changes following chronic treatment with GLP-1 receptor agonists in animal models.

Methods

The effects of chronic treatment with GLP-1 receptor agonists were determined on behavioural parameters [anxiety level in the light–dark compartment test, the motor activity in automated activity cages, immobility in the forced swimming test (FST)] and on corticosterone release in mice. The possible antidepressant effect of chronic liraglutide treatment was also studied in Flinders Sensitive Line (FSL) rats, a genetic model of depression.

Results

Two weeks of treatment with exenatide (10 µg /kg twice daily) or liraglutide (1200 µg/kg once daily) did not affect the anxiety level in a light–dark compartment test nor induce an antidepressant-like effect in the FST in mice. Moreover, chronic treatment with liraglutide had no effect on depression-related behaviour in FSL rats. Interestingly, hypolocomotion induced by the drugs in mice disappeared after chronic dosing. Both of the GLP-1 receptor agonists induced robust increases in corticosterone levels in mice under basal conditions as well as in the case of combination with swimming stress. Remarkably, exenatide was as potent a stimulator of corticosterone release after 2 weeks as after acute administration.

Conclusions

The increases in corticosterone release seen after acute exenatide or liraglutide treatment do not abate after 2 weeks of treatment demonstrating that tolerance does not develop towards this particular effect of GLP-1 agonists.

Keywords

corticosteroneexenatideliraglutideneuroendocrinologystress
Type
Original Articles
Information
Acta Neuropsychiatrica , Volume 27 , Issue 1 , February 2015 , pp. 25 - 32
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Copyright
© Scandinavian College of Neuropsychopharmacology 2014 

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