PDTC Alleviates Depressive Symptoms and Colon Tissue Injury via Inhibiting NO Overproduction in CUMS Rats

BACKGROUND: The accumulated evidence demonstrates that stress plays an important role in the pathogenesis of depression that is associated with intestinal dysfunctions. However, the mechanisms remain unresolved. METHODS: A total of 40 male Wistar rats were obtained and randomly divided into four equal-sized group: control, PDTC + chronic and unpredictable mild stress (CUMS), FLX + CUMS, and CUMS. Western blotting and qRT-PCR were used to examine the levels of nitric oxide (NO), nuclear factor kappa beta (NF-κB), inducible nitric oxide synthase (iNOS), and iNOS mRNA in spinal cord L1-2 and colon. KEY RESULTS: Chronic and unpredictable mild stress increased the serum CORT level, decreased body weight and sucrose preference, and altered OFT performance, while increased levels of NO, iNOS mRNA, iNOS and NF-κB protein in colon and spinal cord were accompanied by histopathological changes in colon. Pretreatment with an NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC), reversed these effects. Fluoxetine failed to prevent NO increase in both spinal cord and colon, while the iNOS protein level, although not statistically significantly increased compared to control, was not decreased compared to CUMS. Also, fluoxetine failed to prevent histological changes. CONCLUSION: In conclusion, the NF-κB/iNOS pathway may be involved in the mechanism of CUMS-induced depressive-like behavior and colon tissue injury.