title: Differential sensitivity to the motor and hypothermic effects of the GABA B receptor agonist baclofen in various mouse strains.
abstract: BACKGROUND
  Comparison of different mouse strains can provide valuable information about the genetic control of behavioural and molecular phenotypes. Recent evidence has demonstrated the importance of GABA B receptors in anxiety and depression. Investigation of the phamacogenetics of GABA B receptor activation may aid in the understanding of mechanisms underlying the role of GABA B in affect.
  
  
  OBJECTIVE
  The aim of current study was to determine the relative sensitivity of different mouse strains to GABA B receptor agonism in two models of GABA B receptor function, namely hypothermia and motor incoordination.
  
  
  METHODS
  Mice each from 11 strains (BALB/cByJIco, DBA/2JIco, OF1, FVB/NIco, CD1, C3H/HeOuJIco, 129/SvPasIco, NMRI, C57BL/6JIco, A/JOlaHsd and Swiss) were trained to walk on a rotarod for 300 s. On the following day, mice received 0, 3, 6 or 12 mg/kg of L: -baclofen PO. Rectal temperature and rotarod performance were measured at 0, 1, 2 and 4 h after drug application.
  
  
  RESULTS
  L: -Baclofen produced a significant dose-dependent hypothermia and ataxia in most, but not all, mouse strains examined. The magnitude and duration of response was influenced by strain, with mice of the 129/SvPasIco strain showing largest hypothermic response to 12 mg/kg l-baclofen and C3H/HeOuJIco the lowest, whereas the BALB/cByJIco strain demonstrated greatest ataxic response on the rotarod, and NMRI the least. Interestingly, some strains (notably C3H/HeOuJIco) had marked differential hypothermic and ataxic responses, with minimal body temperature responses to L: -baclofen but significant ataxia on the rotarod observed.
  
  
  CONCLUSIONS
  There is differential genetic control on specific GABA B receptor populations that mediate hypothermia and ataxia. Further, these studies demonstrate that background strain is an important determinant of GABA B receptor mediated responses, and that hypothermic and ataxic responses may be influenced by independent genetic loci.
authors.affiliation: Novartis Institutes for BioMedical Research, Neuroscience Research, WSJ-386.344, 4002, Basel, Switzerland.
authors.forename: Laura H
authors.initials: LH
authors.lastname: Jacobson
authors.forename: John F
authors.initials: JF
authors.lastname: Cryan
mesh_terms: D000818:Animals; D001418:Baclofen / Q000494:pharmacology* / Q000633:toxicity; D001831:Body Temperature / Q000187:drug effects / Q000235:genetics; D018755:GABA Agonists / Q000494:pharmacology; D058786:GABA-B Receptor Agonists; D007035:Hypothermia / Q000139:chemically induced* / Q000235:genetics*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009048:Motor Skills / Q000187:drug effects* / Q000502:physiology; D018080:Receptors, GABA-B / Q000235:genetics*; D045442:Rotarod Performance Test / Q000379:methods; D013045:Species Specificity
chemical_list: D018755:GABA Agonists; D058786:GABA-B Receptor Agonists; D018080:Receptors, GABA-B; D001418:Baclofen