Several data suggest that the RFamide peptides - especially the prolactin-releasing peptide (PrRP) – play a role in the regulation of stress responses, the disturbances of which can cause many diseases, including depression. PrRP was identified as an endogenous ligand of the GPR10 receptor, but can also bind to the NPFF2 receptor. Here we would like to reveal the association between depressive-like behaviour and changes in the PrRP regulation. Fifteen minutes forced swimming test (FST) was used to induce depression-like symptoms in male Wistar rats. On the next day during a 6 min test we identified vulnerable and resilient animals. At the end of the experiments frozen brain tissues (medulla oblongata, amygdala, hypothalamic nuclei) were collected and mRNA levels were evaluated by rtPCR. In naive animals RNAscope technique was combined with immunohistochemical staining to characterize the PrRP-containing cells.The rtPCR analysis revealed a reduction in the expression of the NPFFR2, the non-specific PrRP receptor on the ventromedial hypothalamic nucleus (VMN) of vulnerable animals in comparison to controls, and resilient rats. In accordance with the literature the strongest PrRP mRNA expression was found in the A1 region by RNAscope in situ hybridization. We could simultaneously detect PrRP mRNA and protein in the amygdala and in the VMN. Furthermore, we revealed that the PrRP mRNS signal colocalized with CRH in the A1 region.Our results support that PrRP and their receptors might play an important role in the regulation of stress and thereby influence the development of stress-related psychological symptoms, primarily depression.