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.