Pharmacological activation of RXFP3 is not orexigenic in C57BL/6J mice

The neuropeptide relaxin-3 and its cognate G-protein-coupled receptor, RXFP3, have been implicated in the control of feeding behaviour in rats. For example, relaxin-3-positive projections and RXFP3 are present within hypothalamic feeding circuits, and icv injection of human relaxin-3 (-0.2 to 1.0 nmol) robustly increases feeding behaviour in satiated rats. To explore whether this action is conserved in other experimental species, the present study examined feeding behaviour in C57BL/6J mice following RXFP3 modulation, as mice display near identical regional distribution patterns of relaxin-3/RXFP3, and relaxin-3/RXFP3 signalling has been shown to modulate behavioural arousal in both species. Central injection of the RXFP3 agonists R3/I5 or H3 relaxin (0.5 nmol, icv) did not alter chow consumption in satiated mice relative to vehicle controls, during the 60 min after treatment. Furthermore, relaxin-3 knockout mice displayed similar basal 24-h chow consumption and 1-h palatable food consumption to wildtype littermate controls; although further studies involving acute pharmacological antagonism of RXFP3 in WT mice are required to eliminate the likelihood of compensation in these life-long relaxin-3 deficient mice. Taken together, these findings are in contrast to the potent orexigenic effects of RXFP3 activation observed in rats, and may reflect differential RXFP3 expression within hypothalamic neuron populations in the rat and mouse, or differences in signalling upstream or downstream of relaxin-3/RXFP3 networks in these two species.