Behavioral phenotyping of mixed background (129S5:B6) relaxin-3 knockout mice

Experimental studies in rats have revealed that the neuropeptide relaxin-3 modulates feeding and metabolism, stress responses, arousal, and exploratory behavior. In the present study, two cohorts of mixed background (129S5:B6) relaxin-3 knockout (KO) and wild-type littermate mice were subjected to a series of behavioral tests. Relaxin-3 KO mice appeared healthy and displayed no genotype differences in body weight, motor coordination (as determined via the rotarod), anxiety (light/dark box, elevated plus maze, large open field), spatial memory (Y-maze), or sensorimotor gating (prepulse inhibition). Female KO mice did, however, display hypoactivity, reflected by significantly shorter distances traveled in the automated locomotor cell, large open field, and novel object tests, and had fewer encounters with a novel mouse in a social interaction test. Male KOs, on the other hand, displayed a "hypersensitivity" to stress, spending longer in the Porsolt posture during a repeated forced swim test and losing a significantly greater percentage of their body weight in response to an 8-week chronic stress regimen. These findings support the hypothesis that relaxin-3 signaling contributes to the central control of arousal, exploratory behavior and stress responses.