Genetic predisposition to anxiety-related behavior predicts predator odor response

While rodents have a keen sense of smell and largely depend on olfactory cues for operating in their environment, most of the widely used tests to assess anxiety-related behavior largely ignore the olfactory system, being primarily based on fear of brightly lit, novel and open spaces. Here, we aimed at testing whether the genetic predisposition to anxiety predicts the predator odor response in mice. In the first experiment, using the 3-chamber avoidance test in CD-1 mice, trimethylthiazoline (TMT), a synthetic fox fecal odor, was shown to induce stronger behavioral and neuroendocrine effects than cat odor and butyric acid, respectively, and was therefore chosen as aversive odor for the following series of experiments. In this series, bidirectionally, selectively inbred CD-1 mice with either high (HAB), intermediate (NAB) or low (LAB) anxiety-related behavior responded differently to TMT, with HABs spending significantly less time than both NABs and LABs in the chamber harbouring the predator odor. Importantly, this result is not confounded by any deficit of the olfactory system, as LAB and NAB mice, while not or only moderately responding to TMT, responded to both the pleasant odor of female urine and the repugnant odor of butyric acid. Probably due to the strength of TMT, a similar increase in corticosterone levels upon predator odor exposure was observed in all three groups. Together, the results suggest that, dependent on the genetic predisposition to extremes in anxiety-related behavior, mice differentially interpret the odor of a potential predator, making this type of avoidance behavior highly predictable.