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

GLUCAGON-like peptide 1; HYPOGLYCEMIC agents; CORTICOSTERONE; LABORATORY mice; MENTAL depression; HUMAN locomotion

ObjectiveGlucagon-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.MethodsThe 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.ResultsTwo 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.ConclusionsThe 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. [ABSTRACT FROM AUTHOR]

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