Gabra5-gene haplotype block associated with behavioral properties of the full agonist benzodiazepine chlordiazepoxide

Y Clément; L Prut; F Saurini; Y S Mineur; A-M Le Guisquet; S Védrine; C Andres; G Vodjdani; C Belzung

doi:10.1016/j.bbr.2012.05.041

Gabra5-gene haplotype block associated with behavioral properties of the full agonist benzodiazepine chlordiazepoxide

Behav Brain Res. 2012 Aug 1;233(2):474-82. doi: 10.1016/j.bbr.2012.05.041. Epub 2012 Jun 4.

Authors

Y Clément¹, L Prut, F Saurini, Y S Mineur, A-M Le Guisquet, S Védrine, C Andres, G Vodjdani, C Belzung

Affiliation

¹ Centre de Recherche de l'Institut du Cerveau et de la Moelle Epinière, 75651 Paris Cedex, France. [email protected]

PMID: 22677273
DOI: 10.1016/j.bbr.2012.05.041

Abstract

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.

MeSH terms

Adaptation, Psychological / drug effects
Adaptation, Psychological / physiology
Animals
Behavior, Animal / drug effects*
Benzodiazepines / agonists*
Benzodiazepines / metabolism
Carrier Proteins / genetics
Cerebral Cortex / drug effects
Cerebral Cortex / metabolism
Chlordiazepoxide*
Dose-Response Relationship, Drug
Gene Expression Regulation / drug effects*
Gene Expression Regulation / genetics
Haplotypes / genetics
Hippocampus / drug effects
Hippocampus / metabolism
Male
Maze Learning / drug effects
Membrane Proteins / genetics
Mice
Mice, Inbred C57BL
Mice, Mutant Strains
Motor Activity / drug effects
Motor Activity / genetics
Mutation / genetics*
RNA, Messenger / metabolism
Reaction Time / drug effects
Reaction Time / genetics
Receptors, GABA-A / genetics*
Rotarod Performance Test
Space Perception / drug effects
Space Perception / physiology

Substances

Carrier Proteins
Gabra5 protein, mouse
Membrane Proteins
RNA, Messenger
Receptors, GABA-A
Benzodiazepines
P protein, mouse
Chlordiazepoxide