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Neuroscience Journal
Volume 2013 (2013), Article ID 736439, 8 pages
Research Article

The mGlu2/3 Receptor Agonists LY354740 and LY379268 Differentially Regulate Restraint-Stress-Induced Expression of c-Fos in Rat Cerebral Cortex

1Neuroscience Discovery, Eli Lilly & Company, Indianapolis, IN 46285, USA
2Neurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, 2100 Copenhagen, Denmark
3Abbott Laboratories, Global Pharmaceutical Research and Development, Neuroscience Clinical Development, Abbott Park, IL 60064-6075, USA

Received 11 June 2013; Accepted 27 September 2013

Academic Editor: Dong-ho Youn

Copyright © 2013 M. M. Menezes et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Metabotropic glutamate 2/3 (mGlu2/3) receptors have emerged as potential therapeutic targets due to the ability of mGlu2/3 receptor agonists to modulate excitatory transmission at specific synapses. LY354740 and LY379268 are selective and potent mGlu2/3 receptor agonists that show both anxiolytic- and antipsychotic-like effects in animal models. We compared the efficacy of LY354740 and LY379268 in attenuating restraint-stress-induced expression of the immediate early gene c-Fos in the rat prelimbic (PrL) and infralimbic (IL) cortex. LY354740 (10 and 30 mg/kg, i.p.) showed statistically significant and dose-related attenuation of stress-induced increase in c-Fos expression, in the rat cortex. By contrast, LY379268 had no effect on restraint-stress-induced c-Fos upregulation (0.3–10 mg/kg, i.p.). Because both compounds inhibit serotonin 2A receptor ( )-induced c-Fos expression, we hypothesize that LY354740 and LY379268 have different in vivo properties and that activation and restraint stress induce c-Fos through distinct mechanisms.