title: Attenuation of ketamine-evoked behavioral responses by mGluR5 positive modulators in mice.
abstract: BACKGROUND
  Recent studies have shown that metabotropic glutamate receptor 5 (mGluR5) can modulate N-methyl-D-aspartate receptor function. Our previous findings demonstrated that the selective mGluR5 agonist (RS)-2-chloro-5-hydroxyphenylglycine (CHPG) and the antagonist 2-methyl-6-(phenylethynyl)-pyridine can reduce and enhance the ketamine anesthesia, respectively.
  
  
  OBJECTIVE
  The purpose of this study was to examine whether CHPG and positive allosteric modulator 3,3'-difluorobenzaldazine (DFB) can reverse ketamine-induced behavioral responses including locomotor hyperactivity, motor incoordination, sensorimotor gating deficit, and learning impairment.
  
  
  METHODS
  Mice were pretreated with CHPG (5-50 nmol,) or DFB (40-100 nmol) followed by ketamine administration. Locomotor activity, rotarod test, prepulse inhibition (PPI) of acoustic startle test, and novel object recognition test were examined.
  
  
  RESULTS
  CHPG and DFB had no effect on these behaviors when administered alone. Both of them attenuated the locomotor hyperactivity, motor incoordination, and cognitive impairment induced by ketamine. However, the ketamine-induced PPI deficit was reversed by CHPG (50 nmol) but not by DFB (up to 100 nmol). CHPG and DFB have distinct potency and efficacy in attenuating ketamine-induced behavioral response.
  
  
  CONCLUSIONS
  These behavioral data extend previous findings and further suggest that positive modulation of mGluR5 may provide a novel approach for development of antipsychotic agents.
authors.affiliation: Institute of Pharmacology and Toxicology, Tzu Chi University, 701, Section 3, Chung-Yang Road, Hualien, 970, Taiwan.
authors.forename: Ming-Huan
authors.initials: MH
authors.lastname: Chan
authors.forename: Pao-Hsiang
authors.initials: PH
authors.lastname: Chiu
authors.forename: Jen-Hou
authors.initials: JH
authors.lastname: Sou
authors.forename: Hwei-Hsien
authors.initials: HH
authors.lastname: Chen
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003072:Cognition Disorders / Q000139:chemically induced / Q000188:drug therapy / Q000523:psychology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D006834:Hydrazines / Q000494:pharmacology; D007276:Injections, Intraventricular; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects; D010648:Phenylacetates / Q000494:pharmacology; D004856:Postural Balance / Q000187:drug effects; D011597:Psychomotor Performance / Q000187:drug effects; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects*; D021641:Recognition, Psychology / Q000187:drug effects; D013216:Reflex, Startle / Q000187:drug effects
chemical_list: C107349:2-chloro-5-hydroxyphenylglycine; C481447:3,3'-difluorobenzaldazine; D018691:Excitatory Amino Acid Antagonists; C578936:Grm5 protein, mouse; D006834:Hydrazines; D010648:Phenylacetates; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D007649:Ketamine; D005998:Glycine