title: Metabotropic glutamate receptor 5 modulates behavioral and hypothermic responses to toluene in rats.
abstract: 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.
authors.affiliation: Department of Pharmacology, Tzu Chi University, 701, Section 3, Chung-Yang Road, Hualien, 97004, Taiwan.
authors.forename: Ming-Huan
authors.initials: MH
authors.lastname: Chan
authors.forename: Chia-Chi
authors.initials: CC
authors.lastname: Lee
authors.forename: Bih-Fen
authors.initials: BF
authors.lastname: Lin
authors.forename: Chia-Yen
authors.initials: CY
authors.lastname: Wu
authors.forename: Hwei-Hsien
authors.initials: HH
authors.lastname: Chen
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D007035:Hypothermia / Q000139:chemically induced* / Q000503:physiopathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology*; D045442:Rotarod Performance Test; D014050:Toluene / Q000633:toxicity*
chemical_list: C578935:GRM5 protein, human; C578937:Grm5 protein, rat; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D014050:Toluene