Feb 18, 2011

Group II mGluR agonist LY354740 and NAAG peptidase inhibitor effects on prepulse inhibition in PCP and D-amphetamine models of schizophrenia

C P ProfaciJoseph H Neale


Group II metabotropic glutamate receptor (mGluR) agonists represent a novel approach to the treatment of schizophrenia. Inasmuch as the peptide neurotransmitter N-acetylaspartylglutamate (NAAG) activates these receptors, NAAG peptidase inhibitors conceptually represent a parallel path toward development of new antipsychotic drugs. While group II agonists are effective in several animal models of schizophrenia, they are reported to lack efficacy in moderating the effects of phencyclidine (PCP) on prepulse inhibition of acoustic startle in animal models of sensory processing deficits found in this disorder. The objective of this study was to re-examine the efficacy of a group II metabotropic glutamate agonist and NAAG peptidase inhibitors in prepulse inhibition models of schizophrenia across two strains of mice. The method used was an assay to determine the efficacy of these drugs in moderating the reduction in prepulse inhibition of acoustic startle in mice treated with PCP and D: -amphetamine. The group II agonist LY354740 (5 and 10 mg/kg) moderated the effects of PCP on prepulse inhibition of acoustic startle in DBA/2 but not C57BL/6 mice. In contrast, two NAAG peptidase inhibitors, ZJ43 (150 mg/kg) and 2-PMPA (50, 100, and 15...Continue Reading

Mentioned in this Paper

C57BL/6 Mouse
Phencyclidine Hydrobromide
Receptors, Metabotropic Glutamate
LY 354740
Bicyclo Compounds

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