Objective: Insect Adipokinetic Hormones (AKH) play role in sugar and lipid mobilization and support the production of energy for the flight and movement of insects. In our previous studies, we showed that AKH had antidepressant, anxiolytic, and analgesic effects in mice and increased neurotrophic factors and neurogenesis in mice, and had beneficial effects in olfactory bulbectomy and posttraumatic stress disorder rat models. In our previous study, we hypothesized that metabolites of AKH, including pyroglutamic acid and pyroglutamyl peptides, pass the blood-brain barrier after intraperitoneal administration of AKH in rats, which is supported by other studies. Methods: In this study, we aimed to investigate the effects of three pyroglutamyl peptides on depression, anxiety, and analgesia in the Forced Swimming Test (FST), Elevated Plus Maze (EPM) test, and hot plate test in mice. We used L-pyroglutamic acid (pGlu; 50 mg/kg), pyroglutamic acid-valine (pGlu-Val; 10 mg/kg), pyroglutamic acid-leucine (pGlu-Leu; 10 mg/ kg) and pyroglutamic acid-valine-aspartate-phenylalanine (pGlu-Val-Asp-Phe; 10 mg/kg) as pyroglutamyl peptides. Results: In FST, all the peptides decreased immobility time, showing that these peptides had antidepressant-like effects. In the EPM test, none of the peptides had a significant effect, but tetrapeptide partially increased both % time spent in the open arm and % entry into the open arm. In the hot plate test, both dipeptides significantly increased latency of licking the arm showing that these dipeptides had analgesic effects. In the open field test, none of the studied peptides altered the total number of crossings compared to the control treatment. Conclusion: In conclusion, we found that pyroglutamyl peptides had preclinical beneficial effects on animal behavior in mice.
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