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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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References

1.Drucker, DJ, Nauck, MA. The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet 2006;368:1696–1705.Google Scholar
2.Ussher, JR, Drucker, DJ. Cardiovascular biology of the incretin system. Endocr Rev 2012;33:187–215.CrossRefGoogle ScholarPubMed
3.Salcedo, I, Tweedie, D, Li, Y, Greig, NH. Neuroprotective and neurotrophic actions of glucagon-like peptide-1: an emerging opportunity to treat neurodegenerative and cerebrovascular disorders. Br J Pharmacol 2012;166:1586–1599.Google Scholar
4.Lockie, SH. Glucagon-like peptide-1 receptor in the brain: role in neuroendocrine control of energy metabolism and treatment target for obesity. J Neuroendocr 2013;25:597–604.CrossRefGoogle ScholarPubMed
5.McKay, NJ, Daniels, D. Glucagon-like peptide-1 receptor agonist administration suppresses both water and saline intake in rats. J Neuroendocr 2013;25:929–938.CrossRefGoogle ScholarPubMed
6.Kanoski, SE, Rupprecht, LE, Fortin, SM, De Jonghe, BC, Hayes, MR. The role of nausea in food intake and body weight suppression by peripheral GLP-1 receptor agonists, exendin-4 and liraglutide. Neuropharmacology 2012;62:1916–1927.Google Scholar
7.Punjabi, M, Arnold, M, Rüttimann, Eet al. Circulating glucagon-like peptide-1 (GLP-1) inhibits eating in male rats by acting in the hindbrain and without inducing avoidance. Endocrinology 2014;155:1690–1699.Google Scholar
8.Labouesse, MA, Stadlbauer, U, Weber, E, Arnold, M, Langhans, W, Pacheco-Lopez, G. Vagal afferents mediate early satiation and prevent flavour avoidance learning in response to intraperitoneally infused exendin-4. J Neuroendocr 2012;24:1505–1516.Google Scholar
9.During, MJ, Cao, L, Zuzga, DSet al. Glucagon-like peptide-1 receptor is involved in learning and neuroprotection. Nat Med 2003;9:1173–1179.Google Scholar
10.Egecioglu, E, Steensland, P, Fredriksson, I, Feltmann, K, Engel, JA, Jerlhag, E. The glucagon-like peptide 1 analogue exendin-4 attenuates alcohol mediated behaviors in rodents. Psychoneuroendocrinology 2013;38:1259–1270.Google Scholar
11.Isacson, R, Nielsen, E, Dannaeus, Ket al. The glucagon-like peptide 1 receptor agonist exendin-4 improves reference memory performance and decreases immobility in the forced swim test. Eur J Pharmacol 2011;650:249–255.Google Scholar
12.Moller, C, Sommer, W, Thorsell, A, Rimondini, R, Heilig, M. Anxiogenic-like action of centrally administered glucagon-like peptide-1 in a punished drinking test. Prog Neuropsychopharmacol Biol Psychiatry 2002;26:119–122.Google Scholar
13.Porsolt, RD, Bertin, A, Jalfre, M. Behavioral despair in mice: a primary screening test for antidepressants. Arch Int Pharmacodyn Ther 1977;229:327–336.Google ScholarPubMed
14.Krass, M, Runkorg, K, Vasar, E, Volke, V. Acute administration of GLP-1 receptor agonists induces hypolocomotion but not anxiety in mice. Acta Neuropsychiatr 2012;24:296–300.Google Scholar
15.Gil-Lozano, M, Perez-Tilve, D, varez-Crespo, Met al. GLP-1(7-36)-amide and exendin-4 stimulate the HPA axis in rodents and humans. Endocrinology 2010;151:2629–2640.Google Scholar
16.Malendowicz, LK, Neri, G, Nussdorfer, GG, Nowak, KW, Zyterska, A, Ziolkowska, A. Prolonged exendin-4 administration stimulates pituitary–adrenocortical axis of normal and streptozotocin-induced diabetic rats. Int J Mol Med 2003;12:593–596.Google ScholarPubMed
17.MacLusky, NJ, Cook, S, Scrocchi, Let al. Neuroendocrine function and response to stress in mice with complete disruption of glucagon-like peptide-1 receptor signaling. Endocrinology 2000;141:752–762.Google Scholar
18.Gil-Lozano, M, Romani-Perez, M, Outeirino-Iglesias, Vet al. Effects of prolonged exendin-4 administration on hypothalamic–pituitary–adrenal axis activity and water balance. Am J Physiol Endocrinol Metab 2013;304:E1105–E1117.Google Scholar
19.Overstreet, DH, Wegener, G. The flinders sensitive line rat model of depression – 25 years and still producing. Pharmacol Rev 2013;65:143–155.Google Scholar
20.Crawley, J, Goodwin, FK. Preliminary report of a simple animal behavior model for the anxiolytic effects of benzodiazepines. Pharmacol Biochem Behav 1980;13:167–170.CrossRefGoogle ScholarPubMed
21.Abildgaard, A, Solskov, L, Volke, V, Harvey, BH, Lund, S, Wegener, G. A high-fat diet exacerbates depressive-like behavior in the Flinders Sensitive Line (FSL) rat, a genetic model of depression. Psychoneuroendocrinology 2011;36:623–633.Google Scholar
22.Detke, MJ, Rickels, M, Lucki, I. Active behaviors in the rat forced swimming test differentially produced by serotonergic and noradrenergic antidepressants. Psychopharmacol 1995;121:66–72.CrossRefGoogle ScholarPubMed
23.Krass, M, Wegener, G, Vasar, E, Volke, V. Antidepressant-like effect of agmatine is not mediated by serotonin. Behav Brain Res 2008;188:324–328.Google Scholar
24.Kinzig, KP, D’Alessio, DA, Herman, JPet al. CNS glucagon-like peptide-1 receptors mediate endocrine and anxiety responses to interoceptive and psychogenic stressors. J Neurosci 2003;23:6163–6170.Google Scholar
25.Ali, S, Stone, MA, Peters, JL, Davies, MJ, Khunti, K. The prevalence of co-morbid depression in adults with type 2 diabetes: a systematic review and meta-analysis. Diabet Med 2006;23:1165–1173.CrossRefGoogle ScholarPubMed
26.Jelsing, J, Vrang, N, Hansen, G, Raun, K, Tang-Christensen, M, Knudsen, LB. Liraglutide: short-lived effect on gastric emptying – long lasting effects on body weight. Diabetes Obes Metab 2012;14:531–538.Google Scholar