A robust animal model of state anxiety: fear-potentiated behaviour in the elevated plus-maze
Section snippets
Different stressors produce fear potentiation in the elevated plus-maze
In the field of anxiety, the elevated plus-maze has become one of the most popular animal models (Pellow et al., 1985). The test involves placing a naive rat (or mouse or pig) in the center of an elevated plus-maze with two open and two enclosed arms, and allowing it to freely explore Rodgers and Cole, 1993, Rodgers and Dalvi, 1997, Andersen et al., 2000. It has been suggested that the reluctance of rats to explore the open arms of the maze is caused by fear of open spaces, rather than the
Stressor controllability and fear-potentiated plus-maze behaviour
To study the effects of stressor controllability on fear-potentiated plus-maze behaviour, an experiment was set up in accordance with the methods of Weiss (1968) on the influence of psychological variables on stress-induced pathology. Three groups were used (Korte et al., 1999). The first group (no stress) of rats received no shocks (see Fig. 1). The second group of rats were trained in a two-way (shuttle box) active avoidance paradigm and were exposed to 10 controllable mild electric footshock
Duration of fear potentiation
To study the duration of fear-potentiated plus-maze behaviour in group-housed rats, they received one inescapable mild footshock (0.6 mA, a.c. for 3 s) (loss of control) (Korte et al., 1999). The next day, the rats were exposed to the prior shock compartment, but no further footshock was given (contextual conditioning). The rats were placed at the following times in the plus-maze: directly, 30 min, 60 min, 90 min, 120 min and 180 min after reexposure to former shock compartment. The control
Classical anxiolytic and anxiogenic drug effects on fear-potentiated plus-maze behaviour in female rats
Previously, we have shown that the classical benzodiazepine anxiolytic diazepam (valium) and the anxiogenic inverse benzodiazepine agonist methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM), respectively, decreased and increased the enhanced anxiety state as measured in the elevated plus-maze in male rats (Korte et al., 1999). To study whether these drug effects were sex-dependent, we used the same drugs in female rats. A similar stress procedure as described in “duration of fear
Corticosteroid involvement in fear-potentiated plus-maze behaviour
To study whether glucocorticosteroids are involved in fear potentiation in the elevated plus-maze test, a similar stress procedure was used as described in Section 3. Male rats were first placed in the prior shock compartment, then injected subcutaneously with vehicle or glucocorticoid receptor antagonist RU38486 or the even more specific glucocorticoid receptor antagonist ORG34580 and 30 min thereafter placed in the elevated plus-maze.
Fig. 5 shows, as expected, that vehicle (0)-treated
CRF involvement in fear-potentiated plus-maze behaviour
In order to show that fear-potentiated plus-maze behaviour is a very robust measure and corticotropin-releasing factor (CRF) receptors are involved in this enhanced anxiety state, we replicated and extended (24 h after defeat) an experiment firstly performed in the Koob laboratory of the Scripps Research Institute at La Jolla (USA) Heinrichs et al., 1992, Koob et al., 1993, Menzaghi et al., 1994. We investigated whether the potent mixed CRF1,2 receptor antagonist d-Phe CRF-(12-41), which was
Allostasis, allostatic state and allostatic load in relation to enhanced anxiety
Allostasis refers to the integrative adaptive processes maintaining stability through change Sterling and Eyer, 1988, McEwen and Stellar, 1993, McEwen, 1998, McEwen, 2000, Goldstein and McEwen, 2002. By controlling all the mechanisms simultaneously, the brain can enforce its command and introduce experience, memories, anticipation and reevaluation of needs in anticipation of physiological requirements (Koob and Le Moal, 2001). Allostatic state, as defined by Koob and Le Moal (2001), refers to a
Seven reasons why fear-potentiated plus-maze behaviour should be used
The present review clearly shows the many advantages of the use of fear-potentiated plus-maze behaviour as a valuable measure in the understanding of neural mechanisms involved in state anxiety and in the search for novel anxiolytics.
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In contrast to the normal elevated plus-maze, which measures innate fear of open spaces, fear-potentiated plus-maze behaviour reflects an enhanced anxiety state (allostatic state).
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Depending on the stressor used (e.g., fear of shock; predator odour, swim stress,
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