The Antidepressant Potential of <i>Heracleum persicum</i> Essential Oil in the Forced Swim Test in Mice: Involvement of Antioxidant and Monoaminergic Mechanisms

Background: Previous studies have highlighted the significant role of oxidative stress in depression. Conversely, Heracleum persicum has demonstrated notable antioxidant properties. However, no study has been conducted to explore the antidepressant effects of H. persicum essential oil (HPEO) and its mechanisms of action. Objectives: This study investigates the antidepressant potential of HPEO in a forced swim test (FST). Methods: In this study, mice (22 - 28 g) were administered HPEO (125 - 500 mg/kg, i.p.) one hour before performing the FST. Additionally, mouse serum levels of glutathione (GSH), catalase (CAT), and nitric oxide (NO) were measured. To assess the role of the monoaminergic system in the mechanism of action of the essential oil, various receptor antagonists were administered one hour before HPEO (500 mg/kg). Results: The HPEO (500 mg/kg) increased serum CAT and GSH levels and decreased NO levels. Acute administration of HPEO (250 and 500 mg/kg) reduced immobility in the FST without significantly altering the animals' locomotion in the open field test (OFT). Pretreatment of the mice with sulpiride, haloperidol, SCH23390, yohimbine, prazosin, p-chlorophenylalanine (pCPA), WAY100135, ketanserin, prazosin, and reserpine restrained the antidepressant potential of HPEO. Conclusions: For the first time, this research demonstrates the antidepressant potential of HPEO, which appears to be mediated by dopaminergic, serotonergic, and noradrenergic systems, as well as antioxidant mechanisms in the FST.