Genetic determinants of sensitivity to diazepam in inbred mice.
Mice from 15 standard inbred strains were tested for sensitivity to several effects of acute diazepam (DZ). Strains differed in sensitivity to DZ-induced: low-dose stimulation and high-dose depression of locomotor activity, hypothermia, and ataxia assessed on a rotarod. Correlations among strain means indicated that sensitivity to a particular effect of DZ generalized well across doses. Sensitivities to some of the different behavioral responses also were significantly correlated. For example, strains sensitive to DZ-induced increases in activity were significantly less sensitive to the drug's hypothermic effects. These results suggest that there are multiple genetic determinants of behavioral sensitivity to DZ effects. That is, genetically influenced sensitivity to DZ is not monolithic but is somewhat specific to the particular response variable studied, a result that also characterizes genetic control of responses to other drugs.
Department of Behavioral Neuroscience, Oregon Health Sciences University, Veterans Affairs Medical Center, Portland 97201, USA. crabbe@ohsu.edu
J C
JC
Crabbe
E J
EJ
Gallaher
S J
SJ
Cross
J K
JK
Belknap
D000704:Analysis of Variance; D000818:Animals; D014151:Anti-Anxiety Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D001259:Ataxia / Q000139:chemically induced / Q000235:genetics; D001921:Brain / Q000378:metabolism; D003975:Diazepam / Q000493:pharmacokinetics / Q000494:pharmacology*; D004198:Disease Susceptibility; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance / Q000235:genetics; D018476:Hypokinesia / Q000139:chemically induced / Q000235:genetics; D007035:Hypothermia / Q000139:chemically induced / Q000235:genetics; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains / Q000235:genetics*; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics; D013045:Species Specificity
D014151:Anti-Anxiety Agents; D003975:Diazepam