Abstract
Methods Mice were randomly divided into experimental groups as follows: the control group received normal saline and MS groups received normal saline, limonene (10 and 20 mg/kg), L-NAME (10 mg/kg), L-arginine (L-arg) (75 mg/kg), limonene (10 mg/kg) plus L-NAME, and limonene (20 mg/kg) plus L-arg. Behavioral tests including the forced swimming test (FST), open field test (OFT), and splash test were performed. Finally, serum and hippocampal nitrite levels as well as the expression of inflammatory genes (IL-1β and TNF-α) in the hippocampus were measured. Results We showed that MS caused depressive-like behavior. Treatment of MS mice with limonene reduced the duration of immobility time in FST and increases the grooming activity time in the splash test. Limonene also reduces serum and brain nitrite levels and reduces the expression of IL-1β and TNF-α in the hippocampus. We found that L-NAME potentiated the effects of a subeffective dose of limonene. Conclusion We concluded that the antidepressant-like effects of limonene are probably mediated through inhibition of neuroinflammation and attenuation of nitrite levels in the hippocampus.
Highlights
Depression is one of the most common psychiatric disorders that is a common and important cause of disability in the world [1, 2]
The results showed that maternal separation (MS) significantly increased the immobility time in the forced swimming test (FST) (P < 0:001, Figure 2)
Concomitant administration of limonene plus L-NAME to the MS mice significantly reduced the duration of immobility compared to the Immobility time Control
Summary
Depression is one of the most common psychiatric disorders that is a common and important cause of disability in the world [1, 2]. Previous studies have shown that oxidative and nitrosative stresses usually play a key role in the pathophysiology of depression by activating the immune response [7]. In this regard, it has been well determined that nitrite oxide (NO) acts as an activator of neuroinflammatory response [8]. We aimed to evaluate antidepressant-like effect of limonene on a mouse model of maternal separation (MS) focusing on neuroinflammation and NO level in the hippocampus. We concluded that the antidepressant-like effects of limonene are probably mediated through inhibition of neuroinflammation and attenuation of nitrite levels in the hippocampus
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