Pharmacological validation of the free-exploratory paradigm in male Wistar rats: A proposed test of trait anxiety

The free-exploratory paradigm (FEP) has been proposed as a model of trait anxiety for both mice and rats. However, its pharmacological validation has only been carried out for the mice. Thus, the aim of the present study was to pharmacologically validate FEP for Wistar rats, by testing the effects of clinically established anxiolytic and anxiogenic drugs, in four different experiments. In all experiments, male Wistar rats were first tested in FEP to be categorized according to their levels of trait anxiety (high, medium and low). Then, only medium trait anxiety rats were selected to be tested again in FEP, two weeks later, after being pharmacologically treated, according to each experiment as follows: Experiment I: 0.5mg/kg of diazepam (DZP) or vehicle; Experiment II: 20mg/kg of pentylenetetrazole (PTZ) or vehicle; Experiment III: 5mg/kg of fluoxetine (FLX5) or vehicle: and Experiment IV: 0.5mg/kg of fluoxetine (FLX0.5) or vehicle. As a group, the results showed that PTZ and FLX5 increased levels of trait anxiety and reduced locomotor activity, whereas DZP and FLX0.5 decreased levels of trait anxiety, without impairing locomotor activity. These results demonstrate that FEP for rats is able to predict clinical anxiolytic and anxiogenic activities of different drugs, including fluoxetine, which is believed to present a dual effect on anxiety. Therefore, this paradigm can be proposed as an effective method for testing potential trait anxiety-reducing drugs, in rats.