title: Different genes influence toluene- and ethanol-induced locomotor impairment in C. elegans.
abstract: BACKGROUND
  The abused volatile solvent toluene shares many behavioral effects with classic central nervous system depressants such as ethanol. Similarities between toluene and ethanol have also been demonstrated using in vitro electrophysiology. Together, these studies suggest that toluene and ethanol may be acting, at least in part, via common mechanisms.
  
  
  METHODS
  We used the genetic model, Caenorhabditis elegans, to examine the behavioral effects of toluene in a simple system, and used mutant strains known to have altered responses to other CNS depressants to examine the involvement of those genes in the motor effects induced by toluene.
  
  
  RESULTS
  Toluene vapor brings about an altered pattern of locomotion in wild-type worms that is visibly distinct from that generated by ethanol. Mutants of the slo-1, rab-3 and unc-64 genes that are resistant to ethanol or the volatile anesthetic halothane show no resistance to toluene. A mutation in the unc-79 gene results in hypersensitivity to ethanol, halothane and toluene indicating a possible convergence of mechanisms of the three compounds. We screened for, and isolated, two mutations that generate resistance to the locomotor depressing effects of toluene and do not alter sensitivity to ethanol.
  
  
  CONCLUSIONS
  In C. elegans, ethanol and toluene have distinct behavioral effects and minimal overlap in terms of the genes responsible for these effects. These findings demonstrate that the C. elegans model system provides a unique and sensitive means of delineating both the commonalities as well as the differences in the neurochemical effects of classical CNS depressants and abused volatile inhalants.
authors.affiliation: Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA 23298-0613, USA.
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Davies
authors.forename: Ryan I
authors.initials: RI
authors.lastname: Friedberg
authors.forename: Hersh
authors.initials: H
authors.lastname: Gupta
authors.forename: Chung-Lung
authors.initials: CL
authors.lastname: Chan
authors.forename: Keith L
authors.initials: KL
authors.lastname: Shelton
authors.forename: Jill C
authors.initials: JC
authors.lastname: Bettinger
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000187:drug effects / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics*; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D000431:Ethanol / Q000494:pharmacology*; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000235:genetics*; D008124:Locomotion / Q000187:drug effects / Q000235:genetics; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics*; D050827:Syntaxin 1 / Q000235:genetics*; D014050:Toluene / Q000494:pharmacology*; D020692:rab3 GTP-Binding Proteins / Q000235:genetics*
chemical_list: D029742:Caenorhabditis elegans Proteins; D002492:Central Nervous System Depressants; D051036:Large-Conductance Calcium-Activated Potassium Channels; D050827:Syntaxin 1; C494845:slo-1 protein, C elegans; C494215:unc-64 protein, C elegans; D014050:Toluene; D000431:Ethanol; D020692:rab3 GTP-Binding Proteins