Journal
PHYSIOLOGY & BEHAVIOR
Volume 103, Issue 3-4, Pages 376-383Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.physbeh.2011.03.005
Keywords
Bipolar disorder; Mania; Lithium; Olanzapine; Hyperactivity; Sleep; Mice
Categories
Funding
- Department of Zoology
- Vilas Associates Award
- NIH [R01 MH085642]
- NSF [NSF 0921706]
- Division Of Integrative Organismal Systems
- Direct For Biological Sciences [0921706] Funding Source: National Science Foundation
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Bipolar disorder (BPD) is a devastating long-term disease for which a significant symptom is mania. Rodent models for mania include psychostimulant-induced hyperactivity and single gene alterations, such as in the Clock or DAT genes, but there is still a pressing need for additional models. Recently, our lab isolated a line of mice, termed Madison (MSN), that exhibit behavioral characteristics that may be analogous to symptoms of mania. In this study we quantified possible traits for mania and tested the response to common anti-BPD drugs in altering the behavioral profiles observed in this strain. Relative to other mouse lines, MSN mice showed significant elevations of in-cage hyperactivity levels, significant decreases in daytime sleep, and significant increases in time swimming in the forced swim test. In terms of sexual behavior, the MSN mice showed significantly higher number of mounts and a trend toward higher time mounting. In separate studies, olanzapine and lithium (or respective controls) were administered to MSN mice for at least 2 weeks and response to treatments was evaluated. Olanzapine (1 mg/kg/day) significantly decreased in-cage hyperactivity and significantly increased time sleeping. Lithium (0.2-0.4% in food) significantly decreased in-cage hyperactivity. Given the behavioral phenotypes and the response to anti-BPD treatments, we propose that MSN mice may provide a possible new model for understanding the neural and genetic basis of phenotypes related to mania and for developing pharmaceutical treatments. (C) 2011 Elsevier Inc. All rights reserved.
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