Objectives: Patients with occlusal disharmony (OD) may be susceptible to depression. The hypothalamus−pituitary−adrenal axis, 5-HT and 5HT2AR in the prefrontal cortex (PFC), amygdala, and hippocampus are involved in the modulation of emotion and depression. This study investigated whether OD affects the HPA axis and 5-HT system and, subsequently, produces depression-like behaviors in rats. Materials and methods: OD was produced by removing 0.5 and 0.25 mm of hard tissue from the cusps of the maxillary molars in randomly selected sides of Sprague−Dawley rats. CUS involved exposure to 2 different stressors per day for 35 days. OD-, CUS-, and OD + CUS-treated groups and an untreated control group were compared in terms of behavior, endocrine status and brain histology. Results: There were significant differences among the four groups in the behavior tests (p < 0.05), especially in the sucrose preference test, where there was a significant decrease in the OD group compared to the control group. ACTH and CORT concentrations were significantly higher in the OD + CUS group than the control group (p < 0.05). Expression of GR and 5-HT2AR in the PFC, amygdala and hippocampal CA1 was significantly higher in the OD, CUS and OD + CUS groups than the control group (p < 0.05). Conclusion: OD promotes depression-like behaviors through peripheral and central pathways via the HPA axis, GR and 5-HT system.
Keywords: 5-HT system; chronic unpredictable stress; depression-like behavior; hypothalamus–pituitary–adrenal axis; occlusal disharmony.