title: 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.
authors.affiliation: Department of Pharmacology, School of Medicine, University of Thessaly, Mezourlo, P.O. Box 1400, 411-10 Larissa, Greece.
authors.forename: Vasilios
authors.initials: V
authors.lastname: Grivas
authors.forename: Athina
authors.initials: A
authors.lastname: Markou
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Pitsikas
mesh_terms: D000596:Amino Acids / Q000009:adverse effects* / Q000494:pharmacology; D000818:Animals; D001007:Anxiety / Q000139:chemically induced*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000009:adverse effects* / Q000494:pharmacology; D003624:Darkness; D004305:Dose-Response Relationship, Drug; D008124:Locomotion / Q000187:drug effects; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists*
chemical_list: D000596:Amino Acids; D019086:Bridged Bicyclo Compounds, Heterocyclic; C118218:LY 379268; D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2; C102718:metabotropic glutamate receptor 3
keywords: Anxiety; LY379268; Light/dark test; Open field test; Rat; mGlu(2/3) receptor