GLP-1 receptor agonists have a sustained stimulatory effect on corticosterone release after chronic treatment
Date
2015Author
Krass, Maarja
Wegener, Gregers
Volke, Annika
Rünkorg, Kertu
Lund, Sten
Metadata
Show full item recordAbstract
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
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- Faculty of Health Sciences [2377]