Abstract
Rationale
Anxiety is a common disorder in humans that exists in many forms, and animal models of human anxiety are typically employed for the discovery of anxiolytic drugs with human therapeutic potential.
Objectives
Ideally, animal models of anxiety are validated for the detection of both anxiogenic and anxiolytic effects, but most animal models can effectively only measure anxiolytic-like effects. As control animals typically spend small amounts of time in the aversive portion of an apparatus, decreases in time spent in this portion are difficult to detect.
Methods
We have modified an existing test of murine anxiety, the mirrored chamber, and have validated this test using several anxiolytic and anxiogenic drugs. In addition, nine mouse strains were compared on the elevated plus maze and modified mirrored chamber.
Results
Increasing doses of ethanol, diazepam, and pentobarbital produced an anxiolytic-like profile while pentylenetetrazol (PTZ), d-amphetamine, and methyl-6, 7-dimethoxyl-4-ethyl-beta-carboline-3-carboxylate (DMCM) appeared anxiogenic. This modified test also dissociated drug effects on anxiety from those on activity for d-amphetamine and diazepam. The inbred mouse strains tested produced a similar range of scores for time spent on the open arms of the elevated plus maze and voluntary reentry time in the mirrored chamber, with an overall genetic correlation of 0.68.
Conclusions
Since control animals reliably reentered the more aversive portion of the apparatus for 25% of the total time available, the modified mirrored chamber may be able to detect anxiogenic states produced by various stressors and drug withdrawal. Further, the strain differences detected suggest that the modified mirrored chamber will be a valuable tool in the discovery of the genetic bases of anxiety states and disorders.
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Acknowledgements
The authors would like to acknowledge Dr. Tamara J. Phillips, Dr. Pamela Metten, and Nathan Rustay for comments on experiments, and Chia-Hua Yu and Alisha Ketner for technical assistance. This research was supported by two VA Merit Review grants, NIAAA grants T32AA07468 and P50AA10760, and NIDA grant DA05288.
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Kliethermes, C.L., Finn, D.A. & Crabbe, J.C. Validation of a modified mirrored chamber sensitive to anxiolytics and anxiogenics in mice. Psychopharmacology 169, 190–197 (2003). https://doi.org/10.1007/s00213-003-1493-z
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DOI: https://doi.org/10.1007/s00213-003-1493-z