Research Article: Pharmacological Alterations of Anxious Behaviour in Mice Depending on Both Strain and the Behavioural Situation

Date Published: November 11, 2009

Publisher: Public Library of Science

Author(s): Yan Clément, Anne-Marie Le Guisquet, Patrice Venault, Georges Chapouthier, Catherine Belzung, Thomas Burne.

Abstract: A previous study comparing non-emotive mice from the strain C57BL/6/ByJ with ABP/Le mice showed ABP/Le to be more anxious in an open-field situation. In the present study, several compounds affecting anxiety were assayed on ABP/Le and C57BL/6/ByJ mice using three behavioural models of anxiety: the elevated plus-maze, the light-dark discrimination test and the free exploratory paradigm. The compounds used were the full benzodiazepine receptor agonist, chlordiazepoxide, and the antagonist, flumazenil, the GABAA antagonist, bicuculline, the full 5-HT1A agonist 8-OH-DPAT, and the mixed 5-HT1A/5-HT1B agonist, RU 24969. Results showed the effect of the compounds to be dependent on both the strain and the behavioural task. Several compounds found to be anxiolytic in ABP/Le mice had an anxiogenic effect on C57BL/6/ByJ mice. More behavioural changes were observed for ABP/Le in the elevated plus-maze, but the clearest findings for C57BL/6/ByJ mice were observed in the light-dark discrimination apparatus. These data demonstrate that anxious behaviour is a complex phenomenon which cannot be described by a single behavioural task nor by the action of a single compound.

Partial Text: Anxiety is a widespread phenomenon occurring in response to various stressors. In humans, there is not one single syndrome, but several which may explain different anxiety conditions reported and could provide evidence for hypotheses on the involvement of certain biological substrates [1], [2]. Anxiety in animals is less clear, given the obvious difficulty in assessing psychological components, but it has been suggested that anxiety is not a single phenomenon. Studies of rodents have assessed anxiety using animal models of fear, e.g. the light/dark test and the elevated plus-maze paradigm to measure state anxiety, and the free exploratory test to measure trait anxiety [3]–[10].

An animal is usually considered anxious if it spends less time in the lit box of a light-dark apparatus, does less exploration of the open arms of a plus-maze apparatus and spends less time in the novel side of the free exploratory apparatus [4], [8], [15], [36], [43]. Using these three tests, recognised as models of anxiety in rodents, (tables 1, 2 & 3), and a comparative design with and without pharmacological treatment, we studied the anxiety behaviour of two inbred strains, ABP and B6. Saline treated controls showed strain-dependent differences in behaviour, most significantly in the plus-maze model and the free exploratory test. In the plus-maze, ABP mice recorded more entries into the open arms and more head-dippings (table 2), more rearing and grooming (data not included). In the free exploratory test, ABP mice spent more time in the novel side, suggesting they are less anxious (table 3). The behaviour cannot be linked to any difference in the level of locomotion, as not only were there no strain-related differences for entries into the closed arms, but in the free exploratory test, the general activity of B6 mice was higher than ABP mice.



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