Activating metabotropic glutamate receptor-7 attenuates visceral hypersensitivity in neonatal maternally separated rats

Increasing evidence has indicated that metabotropic glutamate receptor-7 (mGluR7) is an important target for reducing anxiety and stress-associated behaviours. Notably, mood disorders exhibit high levels of comorbidity with gastrointestinal dysfunction; however, the role of mGluR7 outside of the central nervous system is currently unknown. Activating mGluR7 likely increases colonic secretory function. Therefore, the present study aimed to evaluate the possible effects of mGluR7 on the visceral hypersensitivity of irritable bowel syndrome (IBS) in rats. The expression levels of mGluR7 were assessed in the colon tissues of rats with neonatal maternal separation (NMS)-induced visceral hypersensitivity using reverse transcription-quantitative polymerase chain reaction, western blotting and immunohistochemistry. In addition, the mGluR7 agonist AMN082 (3 or 10 mg/kg; i.p.) was administered 1 h prior to the visceral hypersensitivity test, and the effects of AMN082 were then observed on the nuclear factor (NF)-B signalling pathway. The mRNA and protein expression levels of mGluR7 were upregulated in the colon mucosa of NMS rats compared with in normal control rats. Notably, administration of AMN082 (10 mg/kg) attenuated colorectal distension (CRD)-induced visceral hypersensitivity in NMS rats. In addition, interleukin-10 and transforming growth factor- mRNA expression levels were upregulated, whereas interferon- mRNA expression levels were downregulated in the NMS + AMN082 group compared with in NMS rats. The number of cluster of differentiation 3(+) T cells in the intestinal mucosa and myeloperoxidase activity were decreased in NMS + AMN082 rats. Furthermore, AMN082 treatment reduced the protein expression levels of phosphorylated-NF-B in the colon tissue of NMS rats. These results indicated that activation of mGluR7 may attenuate CRD-induced visceral hypersensitivity in experimental IBS and reduce the abnormal immune cytokine response. In addition, it was suggested that the role of AMN082 in modulating the inflammatory response may be partially associated with inhibiting NF-B activation. These data suggested that targeting mGluR7 may be useful in the treatment of stress-associated IBS.