Suitability of tamoxifen-induced mutagenesis for behavioral phenotyping.
Tamoxifen-induced mutagenesis via the so-called CreER(T2) fusion enzyme is a key technology for the inducible gene knockout in the adult murine brain. However, it requires a subchronic transient treatment with high doses of the non-selective estrogen receptor antagonist tamoxifen. It has been shown earlier that acute tamoxifen treatment causes behavioral alterations, while the long-term behavioral effects of tamoxifen in mice are so far unknown. Therefore C57BL/6 male mice, a common strain used for targeted mutagenesis and behavioral analyses, were subjected to a tamoxifen treatment protocol as used for inducible mutagenesis in vivo, and analyzed for effects on general behavior (locomotion, exploration), emotional behavior (anxiety, depression) and on learning and memory after a drug-free interval period of 4 weeks. The results demonstrate that a test for depression-like behavior, i.e. the Forced Swim Test, is affected even more than 4 weeks after tamoxifen treatment. In contrast, in all other tests, tamoxifen treated mice showed unaltered behaviors, indicating that the currently established 5-day protocol of tamoxifen treatment (40 mg/kg bid) for inducible mutagenesis has no or little effects on the behavior of C57BL/6 male mice after a latency period of 4 weeks. These results are important for all studies using tamoxifen-induced mutagenesis since this protocol obviously does not evoke alterations in general behaviors such as locomotion, exploration or anxiety-like behaviors, which might confound more complex behavioral analyses, nor does it affect standard tests for learning and memory, such as Morris Water Maze, contextual and cued Fear Conditioning and T-Maze learning.
Vogt
M A
MA
Central Institute of Mental Health Mannheim, University of Heidelberg, Mannheim, Germany.
Chourbaji
S
S
Brandwein
C
C
Dormann
C
C
Sprengel
R
R
Gass
P
P
D000704:Analysis of Variance; D000818:Animals; D001007:Anxiety / Q000188:drug therapy / Q000209:etiology; D001522:Behavior, Animal / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D003213:Conditioning, Psychological / Q000187:drug effects; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005106:Exploratory Behavior / Q000187:drug effects; D005239:Fear / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D016296:Mutagenesis / Q000187:drug effects* / Q000502:physiology; D010641:Phenotype; D011930:Reaction Time / Q000187:drug effects; D013550:Swimming; D013629:Tamoxifen / Q000494:pharmacology*
D004965:Estrogen Antagonists; D013629:Tamoxifen