Differential genetic regulation of motor activity and anxiety-related behaviors in mice using an automated home cage task.
Traditional behavioral tests, such as the open field test, measure an animal's responsiveness to a novel environment. However, it is generally difficult to assess whether the behavioral response obtained from these tests relates to the expression level of motor activity and/or to avoidance of anxiogenic areas. Here, an automated home cage environment for mice was designed to obtain independent measures of motor activity levels and of sheltered feeding preference during three consecutive days. Chronic treatment with the anxiolytic drug chlordiazepoxide (5 and 10 mg/kg/day) in C57BL/6J mice reduced sheltered feeding preference without altering motor activity levels. Furthermore, two distinct chromosome substitution strains, derived from C57BL/6J (host strain) and A/J (donor strain) inbred strains, expressed either increased sheltering preference in females (chromosome 15) or reduced motor activity levels in females and males (chromosome 1) when compared to C57BL/6J. Longitudinal behavioral monitoring revealed that these phenotypic differences maintained after adaptation to the home cage. Thus, by using new automated behavioral phenotyping approaches, behavior can be dissociated into distinct behavioral domains (e.g., anxiety-related and motor activity domains) with different underlying genetic origin and pharmacological responsiveness.
Kas
Martien J H
MJ
Rudolf Magnus Institute of Neuroscience, Department of Neuroscience and Pharmacology, University Medical Center Utrecht, Utrecht, The Netherlands. m.j.h.kas@umcutrecht.nl
de Mooij-van Malsen
Annetrude J G
AJ
Olivier
Berend
B
Spruijt
Berry M
BM
van Ree
Jan M
JM
D000818:Animals; D014151:Anti-Anxiety Agents / Q000627:therapeutic use; D001007:Anxiety / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology*; D001331:Automation / Q000295:instrumentation / Q000379:methods*; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D002707:Chlordiazepoxide / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology*; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008957:Models, Genetic; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics*; D012737:Sex Factors; D013045:Species Specificity
D014151:Anti-Anxiety Agents; D002707:Chlordiazepoxide