Gabra5-gene haplotype block associated with behavioral properties of the full agonist benzodiazepine chlordiazepoxide.
The gabra5 gene is associated with pharmacological properties (myorelaxant, amnesic, anxiolytic) of benzodiazepines. It is tightly located (0.5 cM) close to the pink-eyed dilution (p) locus which encodes for fur color on mouse chromosome 7. We tested the putative role of the gabra5 gene in pharmacological properties of the full non specific agonist chlordiazepoxide (CDP), using behavioral and molecular approaches in mutated p/p mice and wild type F2 from crosses between two multiple markers inbred strain ABP/Le and C57BL/6By strain. From our results, using rotarod, light-dark box, elevated maze and radial arm maze tests, we demonstrate that p/p mice are more sensitive than WT to the sensory motor, anxiolytic and amnesic effect of CDP. This is associated with the presence of a haplotypic block on the murine chromosome 7 and with an up regulation of gabra5 mRNAs in hippocampi of p/p F2 mice.
Centre de Recherche de l'Institut du Cerveau et de la Moelle Epinière, 75651 Paris Cedex, France. yan.clement@upmc.fr
Y
Y
Clément
L
L
Prut
F
F
Saurini
Y S
YS
Mineur
A-M
AM
Le Guisquet
S
S
Védrine
C
C
Andres
G
G
Vodjdani
C
C
Belzung
D000223:Adaptation, Psychological / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001569:Benzodiazepines / Q000819:agonists* / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D002707:Chlordiazepoxide; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D011930:Reaction Time / Q000187:drug effects / Q000235:genetics; D011963:Receptors, GABA-A / Q000235:genetics*; D045442:Rotarod Performance Test; D013028:Space Perception / Q000187:drug effects / Q000502:physiology
D002352:Carrier Proteins; C496250:Gabra5 protein, mouse; D008565:Membrane Proteins; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D001569:Benzodiazepines; C076239:P protein, mouse; D002707:Chlordiazepoxide