PT - JOURNAL ARTICLE AU - Satow, Akio AU - Maehara, Shunsuke AU - Ise, Satoko AU - Hikichi, Hirohiko AU - Fukushima, Miyuki AU - Suzuki, Gentaroh AU - Kimura, Toshifumi AU - Tanaka, Takeshi AU - Ito, Satoru AU - Kawamoto, Hiroshi AU - Ohta, Hisashi TI - Pharmacological Effects of the Metabotropic Glutamate Receptor 1 Antagonist Compared with Those of the Metabotropic Glutamate Receptor 5 Antagonist and Metabotropic Glutamate Receptor 2/3 Agonist in Rodents: Detailed Investigations with a Selective Allosteric Metabotropic Glutamate Receptor 1 Antagonist, FTIDC [4-[1-(2-Fluoropyridine-3-yl)-5-methyl-1<em>H</em>-1,2,3-triazol-4-yl]-<em>N</em>-isopropyl-<em>N</em>-methyl-3,6-dihydropyridine-1(2<em>H</em>)-carboxamide] AID - 10.1124/jpet.108.138107 DP - 2008 Aug 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 577--586 VI - 326 IP - 2 4099 - http://jpet.aspetjournals.org/content/326/2/577.short 4100 - http://jpet.aspetjournals.org/content/326/2/577.full SO - J Pharmacol Exp Ther2008 Aug 01; 326 AB - The functional roles of metabotropic glutamate receptor (mGluR) 1 in integrative brain functions were investigated using a potent and selective mGluR1 allosteric antagonist, FTIDC [4-[1-(2-fluoropyridine-3-yl)-5-methyl-1H-1,2,3-triazol-4-yl]-N-isopropyl-N-methyl-3,6-dihydropyridine-1(2H)-carboxamide], in comparison with the mGluR5 allosteric antagonist and the mGluR2/3 orthosteric agonist in rodents. FTIDC reduced maternal separation-induced ultrasonic vocalization and stress-induced hyperthermia without affecting behaviors in the elevated plus maze. An mGluR5 antagonist, 2-methyl-6-(phenylethynyl)-pyridine (MPEP), and an mGluR2/3 agonist, LY379268 [(1R,4R,5S,6R)-4-amino-2-oxabicyclo[3.1.0]hexane-4,6-dicarboxylic acid], showed anxiolytic activities in these models, suggesting involvement of postsynaptic mGluR1 in stress-related responses comparable with mGluR5 and mGluR2/3. Analgesic effects of FTIDC were seen in the formalin test but not in the tail immersion test. FTIDC selectively blocked methamphetamine-induced hyperlocomotion and disruption of prepulse inhibition, whereas MPEP and LY379268 did not alter those behaviors, suggesting that pharmacological blockade of mGluR1 could result in antipsychotic-like effects. FTIDC did not elicit catalepsy or impair motor functions at 10 times higher dose than doses showing antipsychotic-like action. In conclusion, blockade of mGluR1 showed antipsychotic-like effects without impairing motor functions, whereas blockade of mGluR5 and activation of mGluR2/3 did not display such activities. The American Society for Pharmacology and Experimental Therapeutics