EN
BACKGROUND AND AIMS: Relaxin-3 (RLN3) is recently discovered orexigenic peptide expressed in the brainstem. Neurons synthesizing RLN3 are highly responsive to stress factors, which makes RLN3 and its receptor (RXFP3) excellent candidates at the interface of stress- and feeding-related signaling. Hypothalamic paraventricular nucleus (PVN) is considered a main site of action for RXFP3-mediated food intake and weight gain; which appeared linked to inhibition of PVN oxytocin neurons. RLN3 role in appetite control is considered sexually differentiated since increased expression of RLN3 in the NI (associated with reduced c-fos expression in the PVN) was observed only in female binge eating rats. To characterize the RLN3 influence on PVN neurons we conducted in vitro patch clamp recordings. METHODS: Male Wistar rats and Sprague-Dawley rats of both sexes (4–6-week old) were used. Rats were anesthetized and the brains collected for whole cell patch clamp experiment on hypothalamic slices. All drugs were applied via bath perfusion. Immunofluorescent staining was carried out to further characterize recorded neurons. RESULTS: RXFP3-A2 (600 nM) – a selective RXFP3 agonist, inhibited the majority of recorded PVN neurons [the effect persisted in the presence of 0.5 μM TTX, glutamate and GABA receptor blockers (10 μM)]. Moreover, studies on Sprague Dawley PVN neurons indicate discrepancy in proportion of cells responsive to RXFP3 selective agonist with more neurons affected in female than male rats. Importantly, among PVN neurons sensitive to RXFP3 agonist oxytocin-positive cells were present. CONCLUSIONS: Our data support the hypothesis that the relaxin-3/RXFP3 network is associated with feeding control in both male and female rats, indicating higher sensitivity of female rats PVN neurons to RXFP3 activation. Currently we are exploring sexual differences in behavioral effects of hypothalamic RXFP3 activation under different stress and dietary conditions. Funding: NSC, Poland DEC-2012/05D/NZ4/02984 and MSHE, Poland 0020/ DIA/2014/43.