A robust animal model of state anxiety: fear-potentiated behaviour in the elevated plus-maze

Eur J Pharmacol. 2003 Feb 28;463(1-3):163-75. doi: 10.1016/s0014-2999(03)01279-2.


Fear (i.e., decreased percentage time spent on open-arm exploration) in the elevated plus-maze can be potentiated by prior inescapable stressor exposure, but not by escapable stress. The use of fear-potentiated plus-maze behaviour has several advantages as compared to more traditional animal models of anxiety. (a) In contrast to the traditional (spontaneous) elevated plus-maze, which measures innate fear of open spaces, fear-potentiated plus-maze behaviour reflects an enhanced anxiety state (allostatic state). This "state anxiety" can be defined as an unpleasant emotional arousal in face of threatening demands or dangers. A cognitive appraisal of threat is a prerequisite for the experience of this type of emotion. (b) Depending on the stressor used (e.g., fear of shock, predator odour, swim stress, restraint, social defeat, predator stress (cat)), this enhanced anxiety state can last from 90 min to 3 weeks. Stress effects are more severe when rats are isolated in comparison to group housing. (c) Drugs can be administered in the absence of the original stressor and after stressor exposure. As a consequence, retrieval mechanisms are not affected by drug treatment. (d) Fear-potentiated plus-maze behaviour is sensitive to proven/putative anxiolytics and anxiogenics which act via mechanisms related to the benzodiazepine-gamma-aminobutyric acid receptor, but it is also sensitive to corticotropin-releasing receptor antagonists and glucocorticoid receptor antagonists and serotonin receptor agonists/antagonists complex (high predictive validity). (e) Fear-potentiated plus-maze behaviour is very robust, and experiments can easily be replicated in other labs. (f) Fear-potentiated plus-maze behaviour can be measured both in males and females. (g) Neural mechanisms involved in contextual fear conditioning, fear potentiation and state anxiety can be studied.Thus, fear-potentiated plus-maze behaviour may be a valuable measure in the understanding of neural mechanisms involved in the development of anxiety disorders and in the search for novel anxiolytics. Finally, the involvement of corticotropin-releasing factor and corticosteroid-corticotropin-releasing factor interactions in the production of fear-potentiated plus-maze behaviour are discussed.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Anxiety Agents / pharmacology
  • Anxiety / chemically induced
  • Anxiety / physiopathology
  • Anxiety / psychology*
  • Brain / drug effects
  • Brain / physiopathology
  • Exploratory Behavior / drug effects*
  • Fear / drug effects*
  • Fear / physiology
  • Glucocorticoids / metabolism
  • Maze Learning / drug effects*
  • Models, Animal*
  • Receptors, Corticotropin-Releasing Hormone / antagonists & inhibitors
  • Receptors, Corticotropin-Releasing Hormone / metabolism


  • Anti-Anxiety Agents
  • Glucocorticoids
  • Receptors, Corticotropin-Releasing Hormone