Activation of Dopamine D2 Receptor Alleviates Neuroinflammation in a Mouse Model of Allergic Rhinitis With Olfactory Dysfunction

Purpose: Allergic rhinitis (AR) is a common otolaryngology disease and one of the clinical causes of olfactory dysfunction (OD). The olfactory bulb serves as a transfer station for olfactory information transmission, and alleviating its neuroinflammation may be expected to improve AR-induced OD. Recent studies have suggested that the dopamine D2 receptor acts as a key target in regulating immune functions and neuroinflammatory reaction. However, the effect of dopamine D2 receptor on AR-induced neuroinflammation is still unknown. Methods: An AR mouse model with OD induced by ovalbumin were constructed. The buried food pellet test was to evaluate the olfactory function of the mice. Immunofluorescence staining, hematoxylin and eosin staining, enzyme-linked immunosorbent assay and western blotting were also used to investigate the molecular mechanisms underlying the antiinflammatory effects of the dopamine D2 receptor in AR-induced OD. Results: We found that AR-induced OD has a relationship with inflammatory responses in the olfactory bulb. Nasal administration of quinpirole (Quin, a dopamine D2 receptor agonist, 3 mg/kg) improved olfactory function in mice, inhibited the expression of toll-like receptor 4 (TLR4)/nuclear factor-KB (NF-KB) signalings and the levels of tumor necrosis factor-a, interleukin (IL)-113 and IL-6 in the olfactory bulb. In vitro, Quin (20 mu mol/L) inhibited the release of TLR4/NF-KB signalings-dependent inflammatory cytokines in cultured microglia. Conclusions: Activation of the dopamine D2 receptor inhibits the release of inflammatory cytokines through TLR4/NF-KB signaling in the olfactory bulb microglia, and protects olfactory function.