The free-exploratory paradigm: an effective method for measuring neophobic behaviour in mice and testing potential neophobia-reducing drugs.

When given the opportunity to choose between a novel and a familiar compartment (free-exploratory paradigm), BALB/c mice exhibited a preference for familiar places and a marked number of attempts at entry into the novel compartment followed by avoidance responses. In contrast, C57BL/6 mice showed a preference for novel places and very few avoidance responses towards novelty. When novelty was reduced by two familiar odours, fresh sawdust or urine of conspecifics, the neophobia of the BALB/c mice was reversed and the animals clearly showed a preference for the novel compartment. This experimental paradigm can be proposed as an effective animal model for investigating drugs potentially able to reduce neophobia in BALB/c mice. The effects of anxiolytics, effective in the usual animal models of "state" anxiety, were investigated in the free-exploratory paradigm which may model another type of anxiety, termed by Lister (1990) "trait" anxiety. Thus, the behavioural effects of two benzodiazepine full agonists, chlordiazepoxide and diazepam, two non-benzodiazepine partial agonists at benzodiazepine receptors, Ro 19-8022 and alpidem, the 5-HT(1A) receptor agonist, 8-OH-DPAT, and the 5-HT(3) receptor antagonist, zacopride, were assessed in BALB/c and C57BL/6 mice. Chlordiazepoxide, diazepam and Ro 19-8022 completely reversed the preference of BALB/c mice for the familiar compartment, treated animals exhibiting a significant preference for novel places. In contrast, alpidem, 8-OH-DPAT and zacopride did not significantly modify their behaviour. Moreover, the same drugs did not modify the specific responses of C57BL/6 mice toward novelty. These results demonstrate that drugs which bind in a non-selective manner to heterogeneous benzodiazepine recognition sites were very effective in reducing neophobia in BALB/c mice, whereas 5-HT-interacting drugs were unable to counteract their neophobic behaviour. Thus, the free-exploratory paradigm can be proposed as an effective method for testing potential neophobia-("trait" anxiety) reducing drugs.