Consequences of relaxin-3 null mutation in mice on food-entrainable arousal

Abstract

Relaxin-3/RXFP3 networks have been hypothesised to influence behavioural state based on their anatomical distribution and recent experimental findings in rat and mouse. Two arousal- related behaviours altered by changes in relaxin-3/RXFP3 signalling are feeding and voluntary running wheel activity. In particular, relaxin-3 null mutation (knockout) mice display a ‘dark-phase hypoactivity’ phenotype, reflected by reduced voluntary running wheel activity and increased sleeping behaviour, with no other major changes in basal behavioural profile. The present study compared the ability of relaxin-3 deficient (null mutation) and C57BL/6J wildtype littermate mice to entrain daily running wheel activity to timed food availability. Both genotypes adjusted to a restricted feeding paradigm of 3 hours access from ZT6 to ZT9 for 14 days and displayed increased running wheel activity in the 3 hour period prior to scheduled feeding, a phenomena termed food anticipatory activity. No significant difference in running wheel activity was observed between the genotypes, indicating that a whole-of-life relaxin-3 deficiency does not prevent entrainment to a restricted-feeding schedule. Further studies of the precise interaction between relaxin-3/RXFP3 signalling and the other major arousal networks are ongoing, using currently available and new strains of transgenic mice in combination with pharmacological and viral-based methods.