Aprepitant, a NK1 receptor antagonist, improves both airway inflammation and depressive-like behaviors in a rat model with asthma and depression

The objectives of the study were to detect the effect of substance P receptor antagonist aprepitant on a rat model of asthma and depression. Ovalbumin (OVA)-induced asthmatic Wistar rats were exposed to a chronic mild stress (CMS) procedure which was usually used to induce depression in animals. Simultaneously with the CMS, two groups of the rats were respectively given either aprepitant or slaine (p.o.). Pulmonary inflammation was assessed with hematoxylin and eosin staining and inflammatory cell counting in bronchoalveolar lavage fluid (BALF). The depressive-like behaviors were valuated by sucrose solution consumption test and forced swim test. Besides, levels of IL-1β, IL-5, IL-6 IL-13 and IL-17A in serum and lung homogenate, as well as total IgE and OVA-specific IgE in serum were measured using ELISA analysis. We found that the OVA challenge and CMS exposure induced significant lung inflammation, higher levels of total IgE, OVA-specific IgE and inflammatory cytokines (IL-1β, IL-5, IL-6 IL-13 and IL17A) as well as depressive behaviors in rats from the OVA-CMS group. However, NK1 receptor antagonist treatment significantly ameliorated lung inflammation, reduced the elevation of total IgE, OVA-specific IgE and inflammatory cytokines as well as attenuated depressive behaviors in the rats from the aprepitant group if compared to the OVACMS group. These data suggested that NK1 receptor antagonist could improve both asthma and depression in a CMS-asthmatic rat model.