Genotypic differences between C57BL/6 and A inbred mice in anxiolytic and sedative actions of diazepam.
The role of genotype in susceptibility to the behavioral actions of benzodiazepines is not well characterized. To develop a model for such studies, we have characterized the anxiolytic and sedative activities of diazepam in C57BL/6J and A/J inbred mice. C57BL/6J mice were more responsive than A/J mice to diazepam-induced anxiolytic-like activity in the mirrored chamber aversion assay and the elevated plus-maze assay. Basal activity of the two strains did not differ in either assay. In contrast, the two strains were equally responsive to the anxiolytic effects of the 5-HT1A receptor partial agonist, buspirone. C57BL/6J mice were also more susceptible to the sedative effects of diazepam than were A/J mice. Flumazenil blocked the effects of diazepam in these behavioral assays. Measurement of diazepam and nordiazepam in blood and brain suggested that the response differences are of a pharmacodynamic rather than a pharmacokinetic nature. Taken together, these findings indicate that C57BL/6J and A/J mice provide a valuable tool for behavioral genetic studies of the mechanisms underlying the pharmacological actions of benzodiazepines.
Garrett
K M
KM
Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City 73190, USA.
Niekrasz
I
I
Haque
D
D
Parker
K M
KM
Seale
T W
TW
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001143:Arousal / Q000187:drug effects / Q000235:genetics*; D003975:Diazepam / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005838:Genotype; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008805:Mice, Inbred A / Q000235:genetics*; D008810:Mice, Inbred C57BL / Q000235:genetics*; D011985:Receptors, Serotonin / Q000187:drug effects / Q000235:genetics; D044263:Receptors, Serotonin, 5-HT1; D013045:Species Specificity
D014151:Anti-Anxiety Agents; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D003975:Diazepam