Gene-environment interaction influences anxiety-like behavior in ethologically based mouse models.
Ethologically based animal models are widely used; however, results from different laboratories vary significantly which may partly be due to the lack of standardization. Here, we examined the effects of circadian rhythm, lighting condition and mouse strain (BALB/c and C57BL/6, known to differ in measures of avoidance and risk assessment behavior) on two well established behavioral tests in mice: the Elevated Plus Maze (EPM) and the Open Field (OF). Parameters from both paradigms are commonly used as indices of anxiety-like behavior. BALB/c mice and C57BL/6 mice were independently tested in the morning and at night, in regular laboratory lighting and in the dark. We developed a novel method based on infrared lighting from below, coupled to respective video-tracking equipment, which facilitates standard testing of behavior interference-free in complete darkness. The two mouse strains differed in anxiety-related variables for the EPM in the dark, and for the OF in regular laboratory lighting. Moreover, BALB/c displayed greater anxiety-like behavior than C57BL/6 in the OF but less anxiety-like behavior than C57BL/6 in the EPM. Lighting condition has a major influence on both behavioral tests and this to a considerably larger extent than circadian rhythm. In addition, the lighting condition interacts strongly with the genetic background, producing discriminative differences in the anxiety-related variables depending on mouse strain and lighting condition. These results challenge the comparability of not sufficiently standardized tests of anxiety-like behavior and emphasize the need for controlling environmental variables in behavioral phenotyping.
Molecular Psychiatry, Laboratory of Translational Neuroscience, Department of Psychiatry, Psychosomatics, and Psychotherapy, University of Würzburg, Fuechsleinstrasse 15, 97080 Wuerzburg, Germany.
Antonia M
AM
Post
Peter
P
Weyers
Peter
P
Holzer
Evelin
E
Painsipp
Paul
P
Pauli
Thomas
T
Wultsch
Andreas
A
Reif
Klaus-Peter
KP
Lesch
D000704:Analysis of Variance; D000818:Animals; D001007:Anxiety / Q000235:genetics*; D001522:Behavior, Animal / Q000502:physiology*; D002940:Circadian Rhythm / Q000502:physiology; D005106:Exploratory Behavior / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000235:genetics*; D010641:Phenotype; D013045:Species Specificity