Abstract

ABSTRACTPost-traumatic stress disorder (PTSD) is a stress-related mental disorder caused by traumatic experiences. This psychopathological response to traumatic stressors induces anxiety in rats. Oleuropein (OLE), a major compound in olive leaves, reportedly possesses several pharmacological properties, including anti-cancer, anti-diabetic, and anti-atherosclerotic and neuropsychiatric activities. However, the anxiolytic-like effects of OLE and its mechanism of action in PTSD are unclear. The present study used several behavioral tests to examine the effects of OLE on symptoms of anxiety in rats after a single prolonged stress (SPS) exposure by inhibiting the hypothalamic-pituitary-adrenal axis. Male Sprague Dawley rats received OLE (10, 50 and 70 mg/kg, i.p., once daily) for 14 days after SPS exposure. Daily OLE (70 mg/kg) administration significantly increased the number and duration of open arm visits in the elevated plus maze (EPM) test, reduced the anxiety index and grooming behavior in the EPM test, and increased the time spent and number of central zone crossings in the open field test. OLE also blocked the SPS-induced decrease in hippocampal serotonin and neuropeptide Y expression in hippocampus. These findings suggest that OLE has anxiolytic-like effects on behavioral and biochemical symptoms similar to those observed in patients with PTSD.

Highlights

  • Post-traumatic stress disorder (PTSD), a chronic syndrome triggered by exposure to trauma, is characterized by symptoms of intrusive re-experiencing, physiological and psychological hyperarousal, affective numbing, and avoidance of trauma-related stimuli (Kozlovsky et al 2009)

  • The mRNA expression levels of brain-derived neurotrophic factor (BDNF) in hippocampal tissues isolated from four rats per group were determined using reverse transcription-polymerase chain reaction (RTPCR)

  • The administration of OLE after single prolonged stress (SPS) significantly reduced anxiety-like behavior, as indicated by an increase in central zone crossings in the open field test (OFT)

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Summary

Introduction

Post-traumatic stress disorder (PTSD), a chronic syndrome triggered by exposure to trauma, is characterized by symptoms of intrusive re-experiencing, physiological and psychological hyperarousal, affective numbing, and avoidance of trauma-related stimuli (Kozlovsky et al 2009). Many studies have shown that inappropriate adaptation of the HPA axis can lead to pathological states of PTSD, producing serious changes in affective behavior that are indicative of or consistent with anxiety-like symptoms (Shea et al 2005). Oleuropein (OLE), a major phenolic compound in olive leaves, is responsible for these pharmacological properties (Hadrich et al 2016). It improves multiple physiological actions, produces various pharmacological actions in the central nervous system, and has neuroprotective effects in vitro and in vivo (Dekanski et al 2011; Pourkhodadad et al 2016). OLE supplementation at high concentrations significantly decreased body weight, decreased the leptin concentration, and modulated the expression of genes related to obesity in male C57BL/6JOlaHsd mice; it stimulated

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