Does KP-13(6-13) influence rodent behavior similarly to KP-13?
Introduction: Kisspeptins (KPs) are mammalian neuropeptides, ranging from 10 to 54 amino acids in length, regulating the hypothalamic-pituitary-gonadal axis. Short kisspeptin derivatives stimulating the HPG axis have been in the focus of interest, but their behavioral effects have barely been investigated. As KP-13 induced anxiety and decreased pain threshold in our previous experiments, we aimed to investigate the effect of the 8-amino-acid-long KP-13(6-13) on anxiety and nociception as well. Materials and methods: Male Wistar rats and C57Bl/6 mice were implanted with an intracerebroventricular (icv) cannule, through which KP-13(6-13), KP-13 or saline was administered. Anxiety-like behavior was assessed 30 minutes after treatment in rats using the open field (OFT) and elevated plus maze (EPM) tests. Nociception was tested 30, 60 and 120 minutes after treatment in mice using the tail flick test (TFT).Results: In the OFT KP-13(6-13) (0.1 µg) and KP-13 decreased central time and distance, but KP-13(6-13) also promoted immobility and decreased rearing. In EPM KP-13(6-13) (0.1 µg) and KP-13 reduced the percentage of open arm entries and KP-13(6-13) also decreased open arm time and the total number of entries. While KP-13 lowered the pain threshold at 60 minutes, KP-13(6-13) had no significant effect in the TFT. Conclusion: KP-13(6-13) could induce anxiety-like behavior similarly to KP-13, but also promoted immobility and failed to affect nociception, possibly due to altered receptor affinity. Further studies are required to clarify the mechanism of action and to assess if KP-13(6-13) could also stimulate the HPG axis. Acknowledgement: This work was supported by EFOP-3.6.2-16-2017-00006.