Role of 5‐HT1A receptor in insular cortex mediating stress – induced visceral sensory dysfunction

Abstract Background 5‐ HT 1A receptors ( HTR 1As) in the insular cortex are thought to be related with the generation of stress‐induced functional gastrointestinal disorders ( FGID s), but its mechanism is not clear. Visceral hypersensitivity is one important pathophysiological mechanism of FGID s. This study aimed to explore the role of HTR 1As in mediating stress‐induced visceral hypersensitivity and its mechanism in the insular cortex. Methods Visceral hypersensitivity rat model was established by water avoidance stress ( WAS ) and the visceral sensitivity was measured by electromyogram. The activities of HTR 1As were regulated by microinjecting the HTR 1A agonist and antagonist into the insular cortex. The expression levels of 5‐ HT , HTR 1A, N ‐methyl‐ d ‐aspartic acid receptor subtype 2B ( NR 2B) and c‐fos were observed by RT ‐ PCR , Western Blot and immunohistochemical staining. Key Results In WAS rats, the expression levels of 5‐ HT and HTR 1As in the insular cortex were significantly lower ( p < 0.05) than that in sham WAS and normal rats, but the levels of c‐fos and NR 2B were significantly higher ( p < 0.05). After microinjecting HTR 1As agonist into the insular cortex of WAS rats, the visceral sensitivity and the expression levels of NR 2B and c‐fos in insular cortex significantly decreased ( p < 0.05). Conclusions & Inferences The HTR 1As‐ NR 2B signal pathway of insular cortex plays an important role in regulating stress‐induced visceral hypersensitivity.