REVIEW ARTICLESIncreased feeding and body weight gain in rats after acute and chronic activation of RXFP3 by relaxin-3 and receptor-selective peptides functional and therapeutic implicationsGanella, Despina E.a,b; Ryan, Philip J.a,c; Bathgate, Ross A.D.a,b,d; Gundlach, Andrew L.a,c,dAuthor Information aFlorey Neuroscience Institutes bDepartment of Biochemistry and Molecular Biology cDepartment of Anatomy and Neuroscience dFlorey Department of Neuroscience, The University of Melbourne, Victoria, Australia Correspondence to Andrew L. Gundlach, PhD, Florey Neuroscience Institutes, The University of Melbourne, 3010 Victoria, Australia E-mail: [email protected] Received June 12, 2012 Accepted June 25, 2012 Behavioural Pharmacology: September 2012 - Volume 23 - Issue 5 and 6 - p 516-525 doi: 10.1097/FBP.0b013e3283576999 Buy Metrics Abstract This paper provides a review of the effects of relaxin-3 and structurally related analogues on food intake and related behaviours, in relation to hypothalamic neural networks and chemical messengers known to control feeding, metabolism and body weight, including other neuropeptides and hormones. Soon after relaxin-3 was discovered, pharmacological studies identified the ability of the native peptide to stimulate feeding acutely in adult rats. Although interpretation of these data was confounded by ligand cross-reactivity at relaxin-family peptide (RXFP) receptors, studies with relaxin-3 analogues selective for the native relaxin-3 receptor, RXFP3, confirmed that acute and chronic activation of RXFP3 increased feeding and weight gain, and produced changes in plasma leptin and insulin. These studies also identified the hypothalamus as a locus of action. Studies are now required to identify RXFP3-positive neuron populations involved in the effects of relaxin-3/RXFP3 signalling on metabolic and neuroendocrine homeostasis, and to determine whether peptide-based, nonpeptide-based or gene-based RXFP3 treatments can alter food intake and body weight in animal models of obesity and eating disorders, as a reflection of the therapeutic potential of this newly identified transmitter system. © 2012 Lippincott Williams & Wilkins, Inc.