Investigating panic-like defensive behaviors in mice using the beetle mania task.

The beetle mania test (BMT) is a novel ethologically relevant behavioral test which measures the behavior of mice in an enclosed arena in the presence of an erratically moving robotic beetle. When the beetle approaches, the mouse may exhibit either passive behavior, disregarding the stimulus, or active defensive responses, such as escape or flight, which are indicative of panic-like reactions. We compared behavior of 4 different mouse strains in the BMT using undirected jumps as an index of panic-like behavior. Male C57BL/6 mice showed more jumps compared to Balb/c, Swiss, and CD1 strains. Panic-like jumping in C57B1/6 was enhanced when mice were tested in a small (50 cm×25 cm x 37 cm height) compared to the large arena (150 ×25 cm x 37 cm height) suggesting that the smaller arena enhanced perceived threat. Responses in the small arena were attenuated after prior exposure to the test. Panic-like jumping behavior in the small arena was reduced by pre-treatment with the anti-panic agent clonazepam (0.1 mg kg<sup>-1</sup> i.p) and enhanced by treatment with FG-7142 (10 or 20 mg kg<sup>-1</sup> i.p.), an panic-inducing drug. Our findings demonstrate that the BMT in the small arena is a reliable model for evaluating non-respiratory panic-like behaviors and also highlights strain-dependent differences in the expression of these responses, with C57BL/6 mice showing the highest reactivity.