title: The mGlu2/3 Receptor Agonists LY354740 and LY379268 Differentially Regulate Restraint-Stress-Induced Expression of c-Fos in Rat Cerebral Cortex.
abstract: 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 (5-HT2AR)-induced c-Fos expression, we hypothesize that LY354740 and LY379268 have different in vivo properties and that 5-HT2AR activation and restraint stress induce c-Fos through distinct mechanisms.
authors: Neuroscience Discovery, Eli Lilly & Company, Indianapolis, IN 46285, USA.
authors: M M
authors: MM
authors: Menezes
authors: Neurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, 2100 Copenhagen, Denmark.
authors: M A
authors: MA
authors: Santini
authors: Neuroscience Discovery, Eli Lilly & Company, Indianapolis, IN 46285, USA.
authors: M J
authors: MJ
authors: Benvenga
authors: Neuroscience Discovery, Eli Lilly & Company, Indianapolis, IN 46285, USA ; Abbott Laboratories, Global Pharmaceutical Research and Development, Neuroscience Clinical Development, Abbott Park, IL 60064-6075, USA.
authors: G J
authors: GJ
authors: Marek
authors: Neuroscience Discovery, Eli Lilly & Company, Indianapolis, IN 46285, USA.
authors: K M
authors: KM
authors: Merchant
authors: Neurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, 2100 Copenhagen, Denmark.
authors: J D
authors: JD
authors: Mikkelsen
authors: Neuroscience Discovery, Eli Lilly & Company, Indianapolis, IN 46285, USA.
authors: K A
authors: KA
authors: Svensson