Skip to main content

Research Repository

Advanced Search

Preclinical animal anxiety research - flaws and prejudices

Ennaceur, A.; Chazot, P.L.

Preclinical animal anxiety research - flaws and prejudices Thumbnail


A. Ennaceur


The current tests of anxiety in mice and rats used in preclinical research include the elevated plus-maze (EPM) or zero-maze (EZM), the light/dark box (LDB), and the open-field (OF). They are currently very popular, and despite their poor achievements, they continue to exert considerable constraints on the development of novel approaches. Hence, a novel anxiety test needs to be compared with these traditional tests, and assessed against various factors that were identified as a source of their inconsistent and contradictory results. These constraints are very costly, and they are in most cases useless as they originate from flawed methodologies. In the present report, we argue that the EPM or EZM, LDB, and OF do not provide unequivocal measures of anxiety; that there is no evidence of motivation conflict involved in these tests. They can be considered at best, tests of natural preference for unlit and/or enclosed spaces. We also argued that pharmacological validation of a behavioral test is an inappropriate approach; it stems from the confusion of animal models of human behavior with animal models of pathophysiology. A behavioral test is developed to detect not to produce symptoms, and a drug is used to validate an identified physiological target. In order to overcome the major methodological flaws in animal anxiety studies, we proposed an open space anxiety test, a 3D maze, which is described here with highlights of its various advantages over to the traditional tests.


Ennaceur, A., & Chazot, P. (2016). Preclinical animal anxiety research - flaws and prejudices. Pharmacology Research and Perspectives, 4(2),

Journal Article Type Article
Acceptance Date May 4, 2016
Online Publication Date Mar 8, 2016
Publication Date Apr 1, 2016
Deposit Date May 4, 2016
Publicly Available Date May 6, 2016
Journal Pharmacology Research and Perspectives
Publisher Wiley Open Access
Peer Reviewed Peer Reviewed
Volume 4
Issue 2


Published Journal Article (1.4 Mb)

Publisher Licence URL

Copyright Statement
© 2016 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

You might also like

Downloadable Citations