The nitrergic neurotransmission contributes to the anxiolytic-like effect of Citrus sinensis essential oil in animal models.

Citrus fragrances have been used in aromatherapy for the treatment of anxiety, and the essential oil of Citrus sinensis (sweet orange) has shown promising results, although its mechanism of action was not known. The objective of this study was to evaluate the involvement of nitric oxide (NO) neurotransmission in the anxiolytic-like effect of C. sinensis essential oil. Swiss male mice were submitted to 15 min of C. sinensis essential oil inhalation (1%, 2.5%, 5%, and 10%) and tested in the marble-burying test, neophobia-induced hypophagia, and light/dark test. Locomotor activity was evaluated in an automated locomotor activity box. The coadministration of C. sinensis essential oil with L-arginine (200 mg/kg, i.p.), an NO precursor, was used for the behavioral evaluation of nitrergic system mediation. Additionally, the NO synthase activity was measured by nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) analysis in the cerebral cortex. C. sinensis essential oil exerted anxiolytic-like effect at dose that did not change locomotor activity. Moreover, L-arginine pretreatment prevented this anxiolytic-like effect on marble-burying test. Finally, C. sinensis essential oil reduced the NADPH-d positive cells. Thus, the nitrergic neurotransmission plays a relevant role in the anxiolytic-like effect C. sinensis essential oil.

Effects of acute and chronic quercetin administration on methylphenidate-induced hyperlocomotion and oxidative stress.

AIMS: Increases in protein kinase C (PKC) and oxidative stress have been related to mania. Drugs with antioxidant effects or inhibitory actions on PKC may have antimanic effects. The flavonoid quercetin has antioxidant and PKC-inhibiting effects that resemble those of lithium, the first-line treatment for mania in bipolar disorder. We hypothesized that quercetin may have antimanic-like effects in an animal model. MAIN METHODS: In the present study, we investigated the effects of acute and chronic treatment with quercetin (2.5, 5, 10, and 40mg/kg, i.p.) in male Swiss mice that were subjected to methylphenidate (5mg/kg, i.p.)-induced hyperlocomotion, an animal model of mania. Lithium (100mg/kg, i.p.) and diazepam (5mg/kg, i.p.) were used as positive and negative controls, respectively. We also evaluated the effects of these treatments on methylphenidate-induced oxidative stress in the brain by measuring reduced glutathione (GSH) and lipid peroxidation (LPO) levels in the prefrontal cortex, hippocampus, and striatum. KEY FINDINGS: Acute and chronic (21-day) treatment with lithium and diazepam reduced methylphenidate-induced hyperlocomotion. Chronic but not acute treatment with quercetin (10 and 40mg/kg) blocked methylphenidate-induced hyperlocomotion. These effects of lithium and quercetin occurred at doses that did not alter spontaneous locomotor activity, whereas diazepam reduced spontaneous locomotor activity. Chronic treatment with lithium and quercetin blocked the methylphenidate-induced increase in LPO levels in the striatum. SIGNIFICANCE: These results suggest that chronic quercetin treatment has antimanic-like and antioxidant effects, thus encouraging further studies of quercetin as a putative new antimanic drug.

Quercetin reduces manic-like behavior and brain oxidative stress induced by paradoxical sleep deprivation in mice.

Quercetin is a known antioxidant and protein kinase C (PKC) inhibitor. Previous studies have shown that mania involves oxidative stress and an increase in PKC activity. We hypothesized that quercetin affects manic symptoms. In the present study, manic-like behavior (hyperlocomotion) and oxidative stress were induced by 24h paradoxical sleep deprivation (PSD) in male Swiss mice. Both 10 and 40mg/kg quercetin prevented PSD-induced hyperlocomotion. Quercetin reversed the PSD-induced decrease in glutathione (GSH) levels in the prefrontal cortex (PFC) and striatum. Quercetin also reversed the PSD-induced increase in lipid peroxidation (LPO) in the PFC, hippocampus, and striatum. Pearson's correlation analysis revealed a negative correlation between locomotor activity and GSH in the PFC in sleep-deprived mice and a positive correlation between locomotor activity and LPO in the PFC and striatum in sleep-deprived mice. These results suggest that quercetin exerts an antimanic-like effect at doses that do not impair spontaneous locomotor activity, and the antioxidant action of quercetin might contribute to its antimanic-like effects.