Up-regulation of HTR1A reverses stress-induced visceral hypersensitivity through modulating interactions among the anterior cingulate cortex, insular cortex and hippocampus

Abstract Background: This study aimed to explore the effect of 5-HT1A receptors (HTR1A) on activation of the anterior cingulate cortex and simultaneous regulation of neural activity in the insular cortex and hippocampus. Methods: The IBS rat model was established via chronic water avoidance stress (WAS). Visceral sensitivity was measured by electromyogram, and anxiety-like behaviours were evaluated by the open field test. HTR1A-specific lentivirus expressing green fluorescent protein was used to overexpress or down-regulate HTR1A expression. Protein expression levels were detected by western blot. Results: Up-regulation of HTR1A in ACC could inhibit ACC sensitization and reverse the visceral hypersensitivity and anxiety-like behaviours induced by chronic psychological stress. In contrast, down-regulation of HTR1A in ACC might promote these behaviors in IBS rats. Additionally, up-regulation of HTR1A in ACC could inhibit IC and hippocampus sensitization, while down-regulation might have the opposite effect. Conclusions: In IBS rats, HTR1A could modulate ACC activation and interactions among the ACC, IC and hippocampus. These effects might in turn contribute to the development of visceral hypersensitivity and anxiety-like behaviours induced by chronic psychological stress.