Oral Presentation The Annual Scientific Meeting of the Endocrine Society of Australia and the Society for Reproductive Biology 2014

Relaxin-3/RXFP3 signalling promotes motivational drive and stress resilience in mice (#59)

Craig M Smith 1 2 , Ihaia T Hosken 1 2 , Andrew W Walker 1 2 , Berenice E Chua 3 , Cary Zhang 1 2 , Andrew J Lawrence 1 2 , Andrew L Gundlach 1 2 4
  1. Florey Department of Neuroscience and Mental Health; , University of Melbourne, Melbourne, VIC, Australia
  2. The Florey Institute of Neuroscience and Mental Health, Melbourne, VIC, Australia
  3. The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, VIC, Australia
  4. Department of Anatomy and Neuroscience, University of Melbourne, Melbourne, VIC, Australia

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 [1], while relaxin-3/RXFP3 signalling within limbic circuits has been shown to influence complex behaviours [2]. 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 [3]. Furthermore, relaxin-3 and RXFP3 knockout (KO) mice displayed significantly reduced motivation to run on voluntary home-cage running wheels [4], 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.

  1. Ganella DE et al., 2013, Front Neuroendocrinol. 4:128
  2. Smith CM et al., 2014, Front Pharmacol. 5:46
  3. Smith CM et al., 2014, Behav Brain Res. 268:117-26
  4. Smith CM et al., 2012, Gene Brain Behav. 11:94-104