Further pharmacological validation of the BALB/c neophobia in the free exploratory paradigm as an animal model of trait anxiety

Abstract

The present experiments were aimed at investigating the ability of established or putative anxiolytics to reduce the neophobia exhibited by BALB/c mice in the free exploratory paradigm. Results confirm the anxiolytic effects of the benzodiazepine receptor full agonist chlordiazepoxide (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 to a test situation devoid of anxiogenic components, that is to trait anxiety. The non-competitive NMDA antagonist MK 801 (0.04-0.16 mg/kg) elicited very similar behavioural effects. However, the α2-adrenoceptor 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 5HT2 receptor antagonist ritanserin (0.25-4 mg/kg) and the D2 dopaminergic antagonist sulpiride (8-32 mg/kg) failed to decrease neophobia in BALB/c mice. The discussion focuses on the adequacy of this animal model of human pathology. The BALB/c neophobia may not model panic attacks because of the absence of worsening by the panic-provoking agent yohimbine and the lack of attenuation by CCK-B receptor antagonists. Because of its chronicity, this paradigm may model generalized anxiety, a pathology that has been suggested to overlap trait anxiety.