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Pharmacol Biochem Behav. 2012 Dec;103(2):418-24. doi: 10.1016/j.pbb.2012.09.019. Epub 2012 Sep 29.

Metabotropic glutamate receptor 5 modulates behavioral and hypothermic responses to toluene in rats.

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  • 1Department of Pharmacology, Tzu Chi University, 701, Section 3, Chung-Yang Road, Hualien, 97004, Taiwan.


Toluene, a widely used and commonly abused organic solvent, produces various behavioral disturbances in both humans and animals. Blockade of N-methyl-d-aspartate (NMDA) receptors has been suggested to play a critical role in acute toluene-induced behavioral manifestations. Activation of type 5 metabotropic glutamate receptors (mGluR5) attenuates behavioral responses induced by NMDA receptor blockade. The present study elucidated the role of mGluR5 on toluene-induced behavioral and hypothermic responses. Male Sprague-Dawley rats received the mGluR5 agonist (RS)-2-chloro-5-hydroxyphenylglycine (CHPG) or antagonist 6-methyl-2-[phenylethynyl]-pyridine (MPEP) prior to toluene administration. Rotarod test, step-down inhibitory avoidance learning task, and rectal temperature were monitored. Pretreatment of CHPG and MPEP attenuated and potentiated these toluene-induced responses, respectively. In addition, the inhibitory effects of CHPG on toluene-induced motor incoordination, learning impairment, and hypothermia were reversed by the protein kinase C (PKC) inhibitor chelerythrine chloride. These findings suggest that mGluR5 may modulate the neural circuits responsible for motor incoordination, learning impairment, and hypothermic action of toluene through a PKC-dependent signal transduction pathway.

Copyright © 2012 Elsevier Inc. All rights reserved.

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