Regulation of Glutamate and γ-Aminobutyric Acid Receptors in Rats with Depression by Sniffing the Essential Oil of <i>Citrus × aurantium</i> L. [Rutaceae]

Background Modern research has proved that the volatile oil (VO) of Citrus × aurantium L. [Rutaceae] has the effect of treating depression, but the mechanism of treating depression by sniffing has not been studied. Objectives To study the mechanism of VO on depression. Materials and Methods Part I: Except for the blank group, the sniffing group and nasal drip group were continuously administered for 7 days to investigate the optimal administration method. Part II: Except for the blank group, the model, positive group, high, medium, and low dose group of VO were established by chronic unpredictable stress test. The VO was given on the 7th day of modeling for 17 consecutive days. The expression of neurotransmitters and receptors in the brain was determined. The medicinal ingredients in rat brain tissue and blood were detected by gas chromatography–mass spectrometry (GC–MS). Results Compared with nasal drip, sniffing administration has less irritation to the nasal mucosa. The VO could reduce the forced swimming immobility time, adjust the activity state, increase the content of γ-aminobutyric acid (GABA), reduce the content of glutamate, and upregulate the expression of GABAα1, GABAγ2, and their mRNA. The main pharmaceutical component is d-limonene. Conclusion d-limonene in VO upregulates GABAα1, GABAγ2 expression to treat depression.