title: Systemic administration of the potent mGlu8 receptor agonist (S)-3,4-DCPG induces c-Fos in stress-related brain regions in wild-type, but not mGlu8 receptor knockout mice.
abstract: The effect of a novel and potent metabotropic glutamate 8 (mGlu8) receptor agonist, (S)-3,4-dicarboxyphenylglycine (DCPG), was studied in vivo in mouse brain. c-Fos expression was used as a marker of neuronal activity in specific brain regions 2 h after systemic (S)-3,4-DCPG (3-100 mg/kg, i.p.). The selectivity of (S)-3,4-DCPG on mGlu8 receptors was determined in mGlu8 receptor knockout mice. In wild-type mice, (S)-3,4-DCPG (100 mg/kg) significantly increased c-Fos expression in several stress-related brain regions: paraventricular nucleus of the hypothalamus, central nucleus of the amygdala, lateral parabrachial nucleus and locus coeruleus. In the central nucleus of the amgydala, more than 92% of c-Fos positive neurons were identified as GABAergic inhibitory neurons after (S)-3,4-DCPG. Moreover, (S)-3,4-DCPG significantly induced c-Fos in the superficial gray layer of the superior colliculus, a central visual region. c-Fos expression was unchanged by (S)-3,4-DCPG in mGlu8 receptor knockout mice. Our results indicate that systemic (S)-3,4-DCPG alters neuronal excitability in specific brain regions via mGlu8 receptor. The prominent activation of stress areas suggests a role for mGlu8 receptors in the central integration of stress responses. Furthermore, our results indicate that systemic (S)-3,4-DCPG can be used as a tool to explore behavioral and cellular consequences of mGlu8 receptor activation.
authors.affiliation: Eli Lilly and Company, Lilly Corporate Center, drop code 0150, Lilly Research Laboratories, Indianapolis, IN 42685, USA.
authors.forename: Anni-Maija
authors.initials: AM
authors.lastname: Linden
authors.forename: Marcelle
authors.initials: M
authors.lastname: Bergeron
authors.forename: Melvyn
authors.initials: M
authors.lastname: Baez
authors.forename: Darryle D
authors.initials: DD
authors.lastname: Schoepp
mesh_terms: D000818:Animals; D001565:Benzoates / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis* / Q000235:genetics; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000172:deficiency* / Q000235:genetics; D013312:Stress, Physiological / Q000235:genetics / Q000378:metabolism*
chemical_list: C110733:3,4-dicarboxyphenylglycine; D001565:Benzoates; D016760:Proto-Oncogene Proteins c-fos; D018094:Receptors, Metabotropic Glutamate; C111435:metabotropic glutamate receptor 8; D005998:Glycine