title: Group II mGluR agonist LY354740 and NAAG peptidase inhibitor effects on prepulse inhibition in PCP and D-amphetamine models of schizophrenia.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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 150 mg/kg), did not significantly affect the PCP-induced reduction in prepulse inhibition in either strain.
  
  
  CONCLUSIONS
  These data demonstrate that the efficacy of group II agonists in this model of sensory motor processing is strain-specific in mice. The difference between the effects of the group II agonist and the peptidase inhibitors in the DBA/2 mice may relate to the difference in efficacy of NAAG and the agonist at mGluR2.
authors.affiliation: Department of Biology, Georgetown University, 37th and O Sts., NW, Washington, DC 20057, USA.
authors.forename: Caterina P
authors.initials: CP
authors.lastname: Profaci
authors.forename: Kristyn A
authors.initials: KA
authors.lastname: Krolikowski
authors.forename: Rafal T
authors.initials: RT
authors.lastname: Olszewski
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Neale
mesh_terms: D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D003913:Dextroamphetamine; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D018690:Excitatory Amino Acid Agonists / Q000008:administration & dosage / Q000494:pharmacology; D043425:Glutamate Carboxypeptidase II / Q000037:antagonists & inhibitors*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009943:Organophosphorus Compounds / Q000008:administration & dosage / Q000494:pharmacology; D010622:Phencyclidine; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists*; D013216:Reflex, Startle / Q000187:drug effects; D012559:Schizophrenia / Q000188:drug therapy* / Q000503:physiopathology; D013045:Species Specificity; D014508:Urea / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: C402107:2-(phosphonomethyl)pentanedioic acid; D001643:Bridged Bicyclo Compounds; D018690:Excitatory Amino Acid Agonists; D009943:Organophosphorus Compounds; D018094:Receptors, Metabotropic Glutamate; C486211:ZJ43; D014508:Urea; D043425:Glutamate Carboxypeptidase II; D010622:Phencyclidine; C104753:eglumetad; D003913:Dextroamphetamine