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The metabotropic glutamate 2/3 receptor agonist LY379268 induces anxiety-like behavior at the highest dose tested in two rat models of anxiety.

Abstract
The activation of Group II metabotropic glutamate 2/3 (mGlu2/3) receptors reduces the excessive glutamate release that is hypothesized to be associated with neurodegenerative and psychiatric disorders. LY379268 is a highly potent mGlu2/3 receptor agonist that has shown efficacy in several animal models of stroke, epilepsy, drug abuse, schizophrenia, and pain. The present study investigated the effects of LY379268 on anxiety-like behavior in rats assessed in the light/dark and open field tests. The effects of LY379268 on motility in a locomotor activity chamber were also investigated in rats. Administration of the two lower doses of LY379268 used (0.3 and 1mg/kg) did not influence rats' performance either in the light/dark or in the open field test. Importantly, the administration of a higher LY379268 dose (3mg/kg) induced decrease in the number of transitions between the light and dark chambers and time spent in the light chamber compared to the vehicle-treated animals in the light/dark test. In the open field test, rats that received 3mg/kg LY379268 made fewer entries and spent less time in the central zone of the apparatus, exhibited a decrease of rearing episodes, but displayed higher grooming activity compared to controls. Nevertheless, the 3mg/kg dose did not alter locomotor activity compared with vehicle-treated rats in a motility test. The present results indicate that the highest LY379268 dose used in this study induced an anxiety-like effect in the light/dark and open field tests that cannot be attributed to changes in locomotor activity, while lower doses had no effect.
AuthorsVasilios Grivas, Athina Markou, Nikolaos Pitsikas
JournalEuropean journal of pharmacology (Eur J Pharmacol) Vol. 715 Issue 1-3 Pg. 105-10 (Sep 05 2013) ISSN: 1879-0712 [Electronic] Netherlands
PMID23769742 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Copyright© 2013 Elsevier B.V. All rights reserved.
Chemical References
  • Amino Acids
  • Bridged Bicyclo Compounds, Heterocyclic
  • LY 379268
  • Receptors, Metabotropic Glutamate
  • metabotropic glutamate receptor 2
  • metabotropic glutamate receptor 3
Topics
  • Amino Acids (adverse effects, pharmacology)
  • Animals
  • Anxiety (chemically induced)
  • Bridged Bicyclo Compounds, Heterocyclic (adverse effects, pharmacology)
  • Darkness
  • Dose-Response Relationship, Drug
  • Locomotion (drug effects)
  • Male
  • Rats
  • Rats, Wistar
  • Receptors, Metabotropic Glutamate (agonists)

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