Anatomical and functional characterisation of the relaxin-3/RXFP3 system in mice: Modulation of feeding, stress and anxiety — ASN Events
  1. Schedule
  2. Poster Session 1 - Behavioural neuroendocrinology I
  3. Anatomical and functional characterisation of the relaxin-3/RXFP3 system in mice: Modulation of feeding, stress and anxiety

Anatomical and functional characterisation of the relaxin-3/RXFP3 system in mice: Modulation of feeding, stress and anxiety (#150)

Cary Zhang 1 2 , Berenice E Chua 2 , Andrew W Walker 1 2 , Annie Yang 2 , Mouna Haidar 1 2 , Fazel Shabanpoor 2 , Akhter M Hossain 1 2 3 , John D Wade 1 2 3 , Johan K Rosengren 4 , Craig M Smith 1 2 , Andrew L Gundlach 1 2 5
  1. Florey Department of Neuroscience and Mental Health, Melbourne
  2. Florey Institute of Neuroscience and Mental Health, Parkville, Vic, Australia
  3. School of Chemistry, The University of Melbourne, Melbourne
  4. School of Biomedical Sciences, The University of Queensland, Brisbane, Queensland, Australia
  5. Department of Anatomy and Neuroscience, The University of Melbourne, Melbourne

Relaxin-3 is a conserved neuropeptide expressed by neurons in the brainstem nucleus incertus (NI) and periaqueductal gray (PAG), pontine raphe (PnR), and dorsal to substantia nigra (dSN). Ascending relaxin-3 projection patterns to receptor (RXFP3)-rich areas suggest a role in arousal- and stress-related functions including feeding and anxiety1,2. In rats, intracerebroventricular (icv) and intra-PVN infusion of relaxin-3 increased HPA axis activity and feeding3,4, while icv injection of an RXFP3 agonist (RXFP3-A2) reduced anxiety- and depressive-like behaviours5. Notably, similar studies in mice have not been completed. Initial anatomical studies assessed the number of relaxin-3-positive neurons in mouse brain: ~435 in NI, ~70 in PnR, ~115 in PAG, and ~200 in dSN. In functional studies, mice given central injections of RXFP3-A2 (iPVN, 0.1 nmol; icv, 1 nmol), displayed no significant increase in 1-h food intake (iPVN, p=0.63; icv, p=0.49), or altered HPA axis activity (serum corticosterone, iPVN, p=0.33; icv, p=0.55). An RXFP3 antagonist (R3B(1-22)R, 0.4 nmol, icv) did not attenuate serum corticosterone (p=0.89), but reduced food anticipatory activity (p=0.02) and palatable- (p=0.04), post-mild food deprivation- (p<0.001), and dark phase- (p=0.03) food consumption. Effects of RXFP3 activation (RXFP3-A2, 1 nmol, icv) on anxiety behaviour were investigated in multiple tests. No significant differences were observed in time spent in aversive areas, an indicator of anxiety-like behaviour, in the elevated plus maze (p=0.12), large open-field (p=0.84), light/dark box (p=0.45), or social avoidance (p=0.24) tests. However, in the three-chamber social preference test, RXFP3-A2 reduced anxiety-like behaviour, reflected by an increased total interaction with novel mice, compared to vehicle (p=0.04), in mice displaying high, but not low, anxiety. These studies suggest relaxin-3/RXFP3 exerts modulatory effects during high, but not basal, arousal states in mice. Differences between rats and mice may arise from differential RXFP3 expression and/or downstream coupling, and will be further investigated using RXFP3-Cre/YFP reporter mice.

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  2. Smith CM et al. J Comp Neurol 518:4016-4045 (2010)
  3. Watanabe Y et al. J Mol Neurosci 43:169-174 (2011)
  4. McGowan BM et al. Ann NY Acad Sci 1160:250-255 (2009)
  5. Ryan PJ et al. Behav Brain Res 244:142-151 (2013)