Low-dose midazolam attenuates predatory odor avoidance in rats.

Previous studies have shown that predatory odors are a potent anxiogenic stimulus for rodents, yet the ability of benzodiazepines to block odor-induced anxiety remains uncertain. The present study reevaluated this issue using a novel apparatus that, in contrast to previous studies, allowed rats to hide from the odor in a small wooden "hide box" placed within a larger arena. The odor stimulus used was a fabric cat collar that had been worn by a domestic cat for a period of 3 weeks. The experiment was divided into three phases on successive days: 1) habituation, where all rats were placed in the apparatus without cat odor present; 2) conditioning, where rats were presented with the cat odor in the apparatus; and 3) test, where rats previously exposed to the odor were tested for a conditioned avoidance response in the absence of the odor. Results showed that rats exposed to the cat collar displayed a robust avoidance response, spending about 70% of a 20-min session in the hide box compared to 25% in control rats. This avoidance response was completely reversed in rats given a low dose (0.375 mg/kg) of midazolam. During the test phase, rats exposed to the cat odor on the previous day showed elevated levels of hiding when returned to the test apparatus without the cat odor present. This conditioned avoidance was significantly attenuated in rats who had received midazolam (0.375 mg/kg) during cat odor exposure but not in rats given the same dose during the test. These results show that low-dose midazolam is an effective anxiolytic agent in rats during exposure to predatory odor.