The plus-maze discriminative avoidance task: a new model to study memory-anxiety interactions. Effects of chlordiazepoxide and caffeine.

The plus-maze discriminative avoidance paradigm is a new animal model of learning/memory that provides simultaneous information about anxiety. Mice are conditioned to choose between the two enclosed arms (in one of which light and noise are presented as aversive stimuli) while avoiding the two open arms of the apparatus. The test has the advantage of measuring, at the same time and in the same animals, learning/memory (by the percent time spent in aversive enclosed arm - PTAV) and anxiety (by the percent time spent in the open arms - PTO). The effects of chlordiazepoxide and caffeine on learning/memory and anxiety of mice tested in this paradigm were investigated. Chlordiazepoxide (5 mg/kg) significantly increased and caffeine (20 mg/kg) significantly decreased PTO during the training session, suggesting an anxiolytic and an anxiogenic effect, respectively. In the test session, chlordiazepoxide- or caffeine-treated mice presented higher PTAV, suggesting amnestic effects. Given together, chlordiazepoxide plus caffeine did not alter PTO, and the amnesic effect produced by each drug was no longer observed. It is concluded that learning/memory depends on an optimum emotional level. The plus-maze discriminative avoidance model appears to be a useful test to investigate this critical relationship between learning/memory and anxiety.