Subchronic administration of LY354740 does not modify ketamine-evoked behavior and neuronal activity in rats.
Acute treatment with LY354740 {1S,2S,5R,6S-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylate monohydrate}, a potent and selective agonist for group II metabotropic glutamate receptors (mGlu2/3), has previously been shown to block some schizophrenia-like effects of N-methyl-D-aspartate (NMDA) receptor antagonists, suggesting a novel therapeutic strategy for schizophrenia. The present study examined the effects of subchronic pretreatment with LY354740 (0.3, 3 and 10 mg/kg i.p.) on ketamine-evoked (12 mg/kg s.c.) prepulse inhibition deficits, hyperlocomotion and c-fos expression. At all doses, LY354740 failed to reverse both behavioral and neuronal effects of the ketamine. These results therefore do not support the putative antipsychotic role of LY354740.
Imre
Gabor
G
Department of Psychiatry, University Medical Center Groningen, P7.16, University of Groningen, Hanzeplein 1, PO Box 30.001, 9700 RB Groningen, The Netherlands. g.imre@med.umcg.nl
Fokkema
Dirk S
DS
Ter Horst
Gert J
GJ
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D014150:Antipsychotic Agents / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D001643:Bridged Bicyclo Compounds / Q000008:administration & dosage*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007150:Immunohistochemistry; D007649:Ketamine / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D009068:Movement; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012559:Schizophrenia / Q000188:drug therapy
D014151:Anti-Anxiety Agents; D014150:Antipsychotic Agents; D001643:Bridged Bicyclo Compounds; D018691:Excitatory Amino Acid Antagonists; D007649:Ketamine; C104753:eglumetad