THE FREE-EXPLORATORY PARADIGM - AN EFFECTIVE METHOD FOR MEASURING NEOPHOBIC BEHAVIOR IN MICE AND TESTING POTENTIAL NEOPHOBIA-REDUCING DRUGS

When given the opportunity to choose between a novel and a familiar co mpartment (free-exploratory paradigm), BALB/c mice exhibited a prefere nce for familiar places and a marked number of attempts at entry into the novel compartment followed by avoidance responses. In contrast, C5 7BL/6 mice showed a preference for novel places and very few avoidance responses towards novelty. When novelty was reduced by two familiar o dours, fresh sawdust or urine of conspecifics, the neophobia of the BA LB/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 effe cts of two benzodiazepine full agonists, chlordiazepoxide and diazepam , two non-benzodiazepine partial agonists at benzodiazepine receptors, Ro 19-8022 and alpidem, the 5-HT1A receptor agonist, 8-OH-DPAT, and t he 5-HT3 receptor antagonist, zacopride, were assessed in BALB/c and C 57BL/6 mice. Chlordiazepoxide, diazepam and Ro 19-8022 completely reve rsed the preference of BALB/c mice for the familiar compartment, treat ed animals exhibiting a significant preference for novel places. In co ntrast, 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 th at drugs which bind in a non-selective manner to heterogeneous benzodi azepine 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-(''tr ait'' anxiety) reducing drugs.