Vol.:(0123456789) 1 3 International Journal of Peptide Research and Therapeutics https://doi.org/10.1007/s10989-020-10081-z The Efect of RFamide‑Related Peptide‑3 (RFRP‑3 or NPVF) on Food Intake in Neonatal Chickens: The Role of MC3/MC4 and CRF 1 /CRF 2 Receptors Yasaman Moosadoost 1  · Morteza Zendehdel 1  · Mina Khodadadi 1 Accepted: 26 May 2020 © Springer Nature B.V. 2020 Abstract RFamide-related Peptide-3(RFRP-3) plays a key role in appetite regulation. The current study aimed to determine the efect of RFRP-3(Neuropeptide VF) on feeding behavior and its interaction with the melanocortin and corticotropin systems on food intake in the neonatal broiler-type chickens. In experiments 1 and 2, chickens received intracerebroventricular (ICV) injection of control solution besides RFRP-3 (4, 8, and 16 nmol) and RF9 (NPFF receptors antagonist; 4, 8 and 16 nmol) respectively to investigate the efective doses of RFRP-3 and RF9. Experiments 3–8 have been designed to investigate the mediatory role of CRF 1 /CRF 2 and MC3R/MC4R on food intake induced by RFRP-3 in chickens. Finally, in experiments 8–11, the synergistic efect between the MC3R and MC4R with RFRP-3 have been investigated via ICV co-injection of sub- efective doses of RFRP-3 + γ1-MSH and PG-931. Then, cumulative food intake was recorded at 30, 60, and 120 min after injection. According to the results, co-injection of astressin-B and RFRP-3, signifcantly attenuated hypophagic efect of RFRP-3; while astressin2-B reversed this efect of RFRP-3 (p < 0.01). Besides, co-administration of SHU9119 and MCL0020 signifcantly attenuated the hypophagia induced by RFRP-3 in chickens (p < 0.01). However, co-administration of RFRP-3 and PG-931 synergistically decreased food intake in neonatal chicken (p < 0.01). These results suggested hypophagic efect of RFRP-3 is possibly mediated via corticotropin CRF 2 and melanocortin MC4R in neonatal broiler chickens. Keywords Human RFRP-3 · Melanocortin · Corticotropin · Food intake · Chicken Introduction Appetite regulation is one of the complex physiological pro- cedures in animals. Food intake behaviors are modulating by the external (environmental and dietary) and internal fac- tors such as digestive, hormonal, and brain ones (Sharkey et al. 2014). In the central nervous system (CNS), the appe- tite controls by various neurotransmitters and neurological pathways (Parker et al. 2014). RFamide-related peptide-1 (RFRP-1) and RFamide-related peptide-3 (RFRP-3) known as neuropeptide SF (NPSF) and neuropeptide VF (NPVF) respectively are encoded by neuropeptide VF precursor (NPVF) gene that has been already discovered in human, cattle, mice (RFRP-3 only), rats, hamsters, and sheep. Also, it has been reported that RFRP-3 is orthologues to the avian gonadotropin inhibitory hormone (GnIH) (Qi et al. 2009). The RFRP-1 and RFRP-3, belong to the arginine-phenyla- lanine-amide (RF amide) family and 5 peptide groups of this family have been so far identifed. Neuropeptide FF, (PQRFa) PrRP, LPXRFamides (RFRPs), Kisspeptin and QFRP (26RFa), all play a key role in puberty, reproduc- tion activity, bodyweight control and appetite regulation (Tsutsui et al. 2010). Based on the literature, the gene of the NPVF precursor peptide has been located on chro- mosome 2 in chicken (NCBI accession NP_989694) and expression of NPFFr1 to which NPVF binds (NCBI acces- sion NP_989693) (Liu et al. 2001). The short-term anorexic efect of NPVF (human RFRP-3) has been already studied in birds and results showed that its efect is associated with hypothalamic and behavior changes in chickens (Cline et al, 2008). Corticotropin-releasing factor (CRF) is a 41 amino acid neurotransmitter with two G-protein-coupled recep- tors (CRF 1 and CRF 2 ) that have a role in anxiety and stress * Morteza Zendehdel zendedel@ut.ac.ir 1 Department of Basic Sciences, Faculty of Veterinary Medicine, University of Tehran, 14155-6453 Tehran, Iran