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

• Published in: Acta neuropsychiatrica 2015-02, Vol.27 (1), p.25-32
• Main Authors: Krass, Maarja, Volke, Annika, Rünkorg, Kertu, Wegener, Gregers, Lund, Sten, Abildgaard, Anders, Vasar, Eero, Volke, Vallo
• Format: Article
• Language: English
• Subjects: Animals; Antidepressants; Antidiabetics; Anxiety; Behavior, Animal - drug effects; Blood Glucose - drug effects; Corticosterone - blood; Corticosterone - secretion; Drinking water; Drug dosages; Drug Tolerance; GLP-1 receptor agonists; Glucagon; Glucagon-Like Peptide 1 - administration & dosage; Glucagon-Like Peptide 1 - analogs & derivatives; Glucagon-Like Peptide 1 - pharmacology; Glucagon-Like Peptide-1 Receptor; Hypoglycemic Agents - administration & dosage; Hypoglycemic Agents - pharmacology; Laboratory animals; Light; Liraglutide; Male; Mice; Original Articles; Peptides; Peptides - administration & dosage; Peptides - pharmacology; Rats; Receptors, Glucagon - agonists; Stress; Venoms - administration & dosage; Venoms - pharmacology
• ISSN: 0924-2708; 1601-5215
• DOI: 10.1017/neu.2014.36

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. 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. 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. 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.