FURTHER PHARMACOLOGICAL VALIDATION OF THE BALB C NEOPHOBIA IN THE FREE EXPLORATORY PARADIGM AS AN ANIMAL-MODEL OF TRAIT ANXIETY/

The present experiments were aimed at investigating the ability of est ablished or putative anxiolytics to reduce the neophobia exhibited by BALB/c mice in the free exploratory paradigm. Results confirm the anxi olytic effects of the benzodiazepine receptor full agonist chlordiazep oxide (2.5-7.5 mg/kg), of meprobamate (15-60 mg/kg) and of ethanol (0. 5-1.5 g/kg) and extend the pharmacological action of these compounds t o a test situation devoid of anxiogenic components, that is to trait a nxiety. The non-competitive NMDA antagonist MK 801 (0.04-0.16 mg/kg) e licited very similar behavioural effects. However, the alpha 2-adrenoc eptor antagonists yohimbine (0.5-2 mg/kg) and idazoxan (0.3-2.7 mg/kg) , the barbiturate pentobarbital (3.75-30 mg/kg), the mixed 5HT(2) rece ptor antagonist ritanserin (0.25-4 mg/kg) and the D2 dopaminergic anta gonist sulpiride (8-32 mg/kg) failed to decrease neophobia in BALB/c m ice. The discussion focuses on the adequacy of this animal model of hu man pathology. The BALB/c neophobia may not model panic attacks becaus e of the absence of worsening by the panic-provoking agent yohimbine a nd the lack of attenuation by CCK-B receptor antagonists. Because of i ts chronicity, this paradigm may model generalized anxiety, a patholog y that has been suggested to overlap trait anxiety.