D-Limonene decreases depression-like behavior and improves memory via an anti-neuroinflammatory mechanism under chronic restraint stress in rats

Abstract

D-Limonene is a monoterpene compound with anticancer, gastroprotective, anti-inflammatory, antioxidant, anti-nociceptive, and anxiolytic features. In this study, we aimed to investigate the effects of D-limonene under chronic restraint stress in rats. Forty rats were included in the study and randomly divided into 5 groups: i) control, ii) limonene, iii) restraint stress, iv) restraint stress+limonene, and v) restraint stress+fluoxetine, respectively. D-limonene at a dose of 10 mg/kg was administered orally by gavage along with 21 days. At the end of the saline or drug administration, sucrose preference tests, open field tests, novel object recognition tests, and forced swimming test were performed. BDNF, IL-1β, IL-6, and caspase-1 levels were measured from hippocampus tissue. In the sucrose preference test, the consumption rate decreased in the stress group, whereas it increased in the stress+limonene group. In the open field test, traveled distance, mean speed decreased in the restraint stress group, but these values increased in the stress+limonene administered group. In addition, the administration of D-limonene to the restraint stress group were abolished the increased defensive behavior in the stress group in the open field test. In the novel object recognition test, the discrimination index percentage of the restraint stress+limonene group was elevated compared to the stress group. While BDNF levels decreased in the restraint stress group, IL-1β and caspase-1 levels increased compared to the stress +limonene administered group. D-limonene reduces the detrimental effect of stress on learning and memory tests. Also, D-limonene reduces anhedonic and defensive behavior, these effects appear to have antidepressant-like properties.