Antipsychotic action of selective group II metabotropic glutamate receptor agonist MGS0008 and MGS0028 on conditioned avoidance responses in the rat.
The present study was designed to investigate the antipsychotic-like effects of selective group II metabotropic glutamate receptor (mGluR) agonists, 5-[2-[4-(6-fluoro-1H-indole-3-yl) piperidin-1-yl]ethyl]-4-(4-fluorophenyl)thiazole-2-carboxylic acid amide (MGS0008) and (1R, 2S, 5S, 6S)-2-amino-6-fluoro-4-oxobicyclo[3.1.0]hexane-2,6-dicarboxylic acid monohydrate (MGS0028) on conditioned avoidance responses in rats. MGS0008 (1, 3 and 10 mg/kg, p.o.) and MGS0028 (0.3, 1 and 3 mg/kg, p.o.) significantly and reduced conditioned avoidance responses in a dose-dependent fashion. Similar effects were seen with LY418426 (0.3, 1 and 3 mg/kg, p.o.), but not with LY354740 (3, 10 and 30 mg/kg, p.o.), both of which are selective agonists for group II mGluR. Since this effect is seen with a wide range of antipsychotics, such as haloperidol and clozapine [Life Sciences 71 (2002) 947], group II mGluR agonists deserve further attention for possible antipsychotic activity.
Takamori
Kazuaki
K
Research Management Section, Medicinal Research Laboratories, Taisho Pharmaceutical Co. Ltd., 1-403, Yoshino-cho, Saitama, Japan. k.takamori@po.rd.taisho.co.jp
Hirota
Shiho
S
Chaki
Shigeyuki
S
Tanaka
Makoto
M
D000284:Administration, Oral; D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001362:Avoidance Learning / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects*; D001643:Bridged Bicyclo Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D003998:Dicarboxylic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D018690:Excitatory Amino Acid Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists*
D014150:Antipsychotic Agents; D001643:Bridged Bicyclo Compounds; D003998:Dicarboxylic Acids; D018690:Excitatory Amino Acid Agonists; C418123:MGS 0008; D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2; C104753:eglumetad; C418124:MGS 0028