Executive summary

The neuropeptide relaxin-3 and its cognate G-protein-coupled receptor, RXFP3, have been implicat-ed 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 con-served 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 treat-ment. 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 con-trast to the potent orexigenic effects of RXFP3 activation observed in rats, and may reflect differen-tial 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. Key words Relaxin-3, RXFP3, feeding, arousal, motivation, knockou