Hostname: page-component-586b7cd67f-dlnhk Total loading time: 0 Render date: 2024-11-22T21:01:45.946Z Has data issue: false hasContentIssue false
  • English
  • Français

Acute administration of GLP-1 receptor agonists induces hypolocomotion but not anxiety in mice

Published online by Cambridge University Press:  24 June 2014

Maarja Krass ,
Kertu Rünkorg ,
Eero Vasar  and
Vallo Volke
Maarja Krass
Affiliation:
Department of Physiology, University of Tartu, 50411 Tartu, Estonia
Kertu Rünkorg
Affiliation:
Department of Physiology, University of Tartu, 50411 Tartu, Estonia
Eero Vasar
Affiliation:
Department of Physiology, University of Tartu, 50411 Tartu, Estonia
Vallo Volke*
Affiliation:
Department of Physiology, University of Tartu, 50411 Tartu, Estonia
*
Dr Vallo Volke, Department of Physiology, University of Tartu, 19 Ravila Street, 50411 Tartu, Estonia. Tel: +3727374338; Fax: +3727374332; E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Extract

Krass M, Rünkorg K, Vasar E, Volke V. Acute administration of GLP-1 receptor agonists induces hypolocomotion but not anxiety in mice.

Objective: The aim of this study was to compare the behavioural and hormonal effects of systemic (subcutaneous) treatment with glucaemically equipotent doses of exenatide and liraglutide in mice.

Methods: The effects of glucagon-like peptide-1 (GLP-1) receptor agonists were determined on anxiety level in the light–dark compartment test, the motor activity in automated activity cages and finally the forced swimming test was performed.

Results: Both exenatide (1–20 µg/kg) and liraglutide (200–1200 µg/kg) decreased the glucose levels up to 30% in freely fed animals. In glucaemically equipotent doses the drugs induced very similar behavioural and hormonal effects: there was no change on anxiety level or immobility time, however, both drugs suppressed motor activity and increased corticosterone levels.

Conclusion: We conclude that the two clinically approved GLP-1 receptor agonists induce very similar suppression of motor activity and stimulation of corticosterone release in mice.

Keywords

anxietycortisolneuroendocrinologystress
Type
Research Article
Information
Acta Neuropsychiatrica , Volume 24 , Issue 5 , October 2012 , pp. 296 - 300
Copyright
Copyright © Cambridge University Press 2012

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1.Drucker, DJ.The biology of incretin hormones. Cell Metab 2006;3:153–165.CrossRefGoogle ScholarPubMed
2.Williams, DL.Minireview: finding the sweet spot: peripheral versus central glucagon-like peptide 1 action in feeding and glucose homeostasis. Endocrinology 2009;150:2997–3001.CrossRefGoogle ScholarPubMed
3.Tang-Christensen, M, Larsen, PJ, Goke, R et al. Central administration of GLP-1-(7-36) amide inhibits food and water intake in rats. Am J Physiol 1996;271:R848–R856.Google ScholarPubMed
4.During, MJ, Cao, L, Zuzga, DS et al. Glucagon-like peptide-1 receptor is involved in learning and neuroprotection. Nat Med 2003;9:1173–1179.CrossRefGoogle ScholarPubMed
5.Kinzig, KP, D'Alessio, DA, Herman, JP et al. CNS glucagon-like peptide-1 receptors mediate endocrine and anxiety responses to interoceptive and psychogenic stressors. J Neurosci 2003;23:6163–6170.CrossRefGoogle ScholarPubMed
6.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.CrossRefGoogle Scholar
7.Gulec, G, Isbil-Buyukcoskun, N, Kahveci, N.Effects of centrally-injected glucagon-like peptide-1 on pilocarpine-induced seizures, anxiety and locomotor and exploratory activity in rat. Neuropeptides 2010;44:285–291.CrossRefGoogle ScholarPubMed
8.MacLusky, NJ, Cook, S, Scrocchi, L et al. Neuroendocrine function and response to stress in mice with complete disruption of glucagon-like peptide-1 receptor signaling. Endocrinology 2000;141:752–762.CrossRefGoogle ScholarPubMed
9.Gil-Lozano, M, Perez-Tilve, D, Varez-Crespo, M et al. GLP-1(7-36)-amide and Exendin-4 stimulate the HPA axis in rodents and humans. Endocrinology 2010;151:2629–2640.CrossRefGoogle Scholar
10.Kastin, AJ, Akerstrom, V.Entry of exendin-4 into brain is rapid but may be limited at high doses. Int J Obes Relat Metab Disord 2003;27:313–318.CrossRefGoogle ScholarPubMed
11.Kanoski, SE, Fortin, SM, Arnold, M, Grill, HJ, Hayes, MR.Peripheral and central GLP-1 receptor populations mediate the anorectic effects of peripherally administered GLP-1 receptor agonists, liraglutide and exendin-4. Endocrinology 2011;152:3103–3112.CrossRefGoogle ScholarPubMed
12.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
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.Volke, V, Wegener, G, Bourin, M, Vasar, E.Antidepress ant- and anxiolytic-like effects of selective neuronal NOS inhibitor 1-(2-trifluoromethylphenyl)-imidazole in mice. Behav Brain Res 2003;140:141–147.CrossRefGoogle Scholar
15.Strawn, JR, D'Alessio, DA, Keck, PE Jr, Seeley, RJ.Failure of glucagon-like peptide-1 to induce panic attacks or anxiety in patients with panic disorder. J Psychiatr Res 2008;42:787–789.CrossRefGoogle ScholarPubMed
16.Talsania, T, Anini, Y, Siu, S, Drucker, DJ, Brubaker, PL.Peripheral exendin-4 and peptide YY(3-36) synergistically reduce food intake through different mechanisms in mice. Endocrinology 2005;146:3748–3756.CrossRefGoogle ScholarPubMed
17.Porter, DW, Kerr, BD, Flatt, PR, Holscher, C, Gault, VA.Four weeks administration of Liraglutide improves memory and learning as well as glycaemic control in mice with high fat dietary-induced obesity and insulin resistance. Diabetes Obes Metab 2010;12:891–899.CrossRefGoogle ScholarPubMed