The neuropeptide relaxin-3 is expressed by large projection neurons within the pontine nucleus incertus, and signals via its widely expressed G-protein coupled receptor, RXFP3. In rats, exogenous relaxin-3 administration can modulate hypothalamic substrates to stimulate the release of pituitary hormones involved in both stress and reproductive axes , while relaxin-3/RXFP3 signalling within limbic circuits has been shown to influence complex behaviours . In several recent studies we have used wild-type (WT) and transgenic mice to investigate the role of relaxin-3/RXFP3 signalling in this major experimental species. Central infusion of RXFP3 antagonists reduced motivated food seeking (p<0.05) and both regular and palatable food consumption (p<0.001) in WT mice . Furthermore, relaxin-3 and RXFP3 knockout (KO) mice displayed significantly reduced motivation to run on voluntary home-cage running wheels , and to lever press to obtain sucrose rewards in an operant chamber (p<0.05). Further studies revealed that relaxin-3 and RXFP3 KO mice were hypersensitive to stress-induced insomnia (p<0.001) and stress-induced changes in alcohol consumption (p<0.05), respectively. Studies to gain insights into the potential mechanisms which underlie these actions are ongoing, including studies to determine the neurochemical phenotype of RXFP3 neurons using newly established RXFP3-eYFP mice. Together, these data provide evidence that relaxin-3/RXFP3 signalling acts to promote motivational drive and stress resilience. As these modalities are often disrupted in affective disorders such as depression, these studies highlight the potential of RXFP3 as a therapeutic target.