title: GLP-1 receptor agonists have a sustained stimulatory effect on corticosterone release after chronic treatment.
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.
authors.affiliation: 1Department of Physiology,University of Tartu,Tartu,Estonia.
authors.forename: Maarja
authors.initials: M
authors.lastname: Krass
authors.affiliation: 3Department of Dermatology;University of Tartu,Tartu,Estonia.
authors.forename: Annika
authors.initials: A
authors.lastname: Volke
authors.affiliation: 1Department of Physiology,University of Tartu,Tartu,Estonia.
authors.forename: Kertu
authors.initials: K
authors.lastname: Rünkorg
authors.affiliation: 4Translational Neuropsychiatry Unit,Aarhus University,Risskov,Denmark.
authors.forename: Gregers
authors.initials: G
authors.lastname: Wegener
authors.affiliation: 6Medical Department MEA (Endocrinology),Aarhus University Hospital,Aarhus C,Denmark.
authors.forename: Sten
authors.initials: S
authors.lastname: Lund
authors.affiliation: 4Translational Neuropsychiatry Unit,Aarhus University,Risskov,Denmark.
authors.forename: Anders
authors.initials: A
authors.lastname: Abildgaard
authors.affiliation: 1Department of Physiology,University of Tartu,Tartu,Estonia.
authors.forename: Eero
authors.initials: E
authors.lastname: Vasar
authors.affiliation: 1Department of Physiology,University of Tartu,Tartu,Estonia.
authors.forename: Vallo
authors.initials: V
authors.lastname: Volke
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001786:Blood Glucose / Q000187:drug effects; D003345:Corticosterone / Q000097:blood / Q000378:metabolism*; D004361:Drug Tolerance; D000077270:Exenatide; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000067757:Glucagon-Like Peptide-1 Receptor; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology; D000069450:Liraglutide; D008297:Male; D051379:Mice; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D018027:Receptors, Glucagon / Q000819:agonists*; D014688:Venoms / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D001786:Blood Glucose; C000593834:Glp1r protein, mouse; C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D007004:Hypoglycemic Agents; D010455:Peptides; D018027:Receptors, Glucagon; D014688:Venoms; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide; D003345:Corticosterone
keywords: stress