title: The group II metabotropic glutamate receptor agonist LY379268 reduces toluene-induced enhancement of brain-stimulation reward and behavioral disturbances.
abstract: BACKGROUND
  Toluene, a widely abused solvent with demonstrated addictive potential in humans, hasbeen reported to negatively modulate N-methyl-D-aspartate receptors (NMDARs) and alter glutamatergicneurotransmission. The group II metabotropic glutamate receptor (mGluR) agonist LY379268 has beenshown to regulate glutamate release transmission and NMDAR function and block toluene-induced locomotorhyperactivity. However, remaining unknown is whether group II mGluRs are involved in the toluene-induced reward-facilitating effect and other behavioral manifestations.
  
  
  OBJECTIVE
  The present study evaluated the effects of LY379268 on toluene-induced reward enhancement, motor incoordination, recognition memory impairment, and social interaction deficits.
  
  
  RESULTS
  Our data demonstrated that LY379268 significantly reversed the toluene-induced lowering of intracranial self-stimulation (ICSS) thresholds and impairments in novel object recognition, rotarod performance, and social interaction with different potencies.
  
  
  CONCLUSIONS
  These results indicate a negative modulatory role of group II mGluRs in acute toluene-induced reward-facilitating and behavioral effects and suggest that group II mGluR agonists may have therapeutic potential for toluene addiction and the prevention of toluene intoxication caused by occupational or intentional exposure.
authors.affiliation: Institute of Neuroscience, National Chengchi University, 64, Sec. 2, ZhiNan Road, Wenshan District, Taipei City, 11605, Taiwan.
authors.forename: Ming-Huan
authors.initials: MH
authors.lastname: Chan
authors.forename: Yi-Ling
authors.initials: YL
authors.lastname: Tsai
authors.forename: Mei-Yi
authors.initials: MY
authors.lastname: Lee
authors.forename: Astrid K
authors.initials: AK
authors.lastname: Stoker
authors.forename: Athina
authors.initials: A
authors.lastname: Markou
authors.forename: Hwei-Hsien
authors.initials: HH
authors.lastname: Chen
mesh_terms: D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D004567:Electrodes, Implanted; D007398:Interpersonal Relations; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D004856:Postural Balance / Q000187:drug effects; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists*; D021641:Recognition, Psychology / Q000187:drug effects; D012201:Reward; D012653:Self Stimulation / Q000187:drug effects*; D014050:Toluene / Q000037:antagonists & inhibitors* / Q000494:pharmacology*
chemical_list: D000596:Amino Acids; D019086:Bridged Bicyclo Compounds, Heterocyclic; C118218:LY 379268; D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2; D014050:Toluene