Toxicology Research Today is a free monthly online journal that collates and summarizes the latest research about Toxicology, including details on forensic toxicology, carcinogenicity, assays.

Attenuation of ketamine-evoked behavioral responses by mGluR5 positive modulators in mice.

Chan MH, Chiu PH, Sou JH, Chen HH

Institute of Pharmacology and Toxicology, Tzu Chi University, 701, Section 3, Chung-Yang Road, Hualien, 970, Taiwan.

RATIONALE: 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.

Published 1 May 2008 in Psychopharmacology (Berl), 198(1): 141-8.
Full-text of this article is available online (may require subscription).

© 2005-2008 Toxicology Research Today. All Rights Reserved.