TY - JOUR
T1 - Differential sensitivity to the motor and hypothermic effects of the GABAB receptor agonist baclofen in various mouse strains
AU - Jacobson, Laura H.
AU - Cryan, John F.
PY - 2005/5
Y1 - 2005/5
N2 - Rationale: 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 GABAB 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 GABAB in affect. Objectives: The aim of current study was to determine the relative sensitivity of different mouse strains to GABAB receptor agonism in two models of GABAB 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. Conclusion: There is differential genetic control on specific GABAB receptor populations that mediate hypothermia and ataxia. Further, these studies demonstrate that background strain is an important determinant of GABAB receptor mediated responses, and that hypothermic and ataxic responses may be influenced by independent genetic loci.
AB - Rationale: 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 GABAB 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 GABAB in affect. Objectives: The aim of current study was to determine the relative sensitivity of different mouse strains to GABAB receptor agonism in two models of GABAB 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. Conclusion: There is differential genetic control on specific GABAB receptor populations that mediate hypothermia and ataxia. Further, these studies demonstrate that background strain is an important determinant of GABAB receptor mediated responses, and that hypothermic and ataxic responses may be influenced by independent genetic loci.
KW - Ataxia
KW - Baclofen
KW - GABA
KW - Hypothermia
KW - Mouse
KW - Pharmacogenetics
KW - Strain
UR - https://www.scopus.com/pages/publications/18744364177
U2 - 10.1007/s00213-004-2086-1
DO - 10.1007/s00213-004-2086-1
M3 - Article
C2 - 15668819
AN - SCOPUS:18744364177
SN - 0033-3158
VL - 179
SP - 688
EP - 699
JO - Psychopharmacology
JF - Psychopharmacology
IS - 3
ER -