Neuronal nitric oxide synthase in dorsal raphe nucleus mediates PTSD-like behaviors induced by single-prolonged stress through inhibiting serotonergic neurons activity

The pathogenesis of post-traumatic stress disorder (PTSD) remains largely unclear. A large body of evidence suggests that the abnormal level of serotonin (5-HT) is closely related to the onset of PTSD. Several reports reveal that nitric oxide (NO) affects extracellular 5-HT levels in various brain regions, but no consistent direction of change was found and the underlying mechanisms remain unknown. The most of serotonergic neurons in dorsal raphe nucleus (DRN), a major source of serotonergic input to the forebrain, co-expresses neuronal nitric oxide synthase (nNOS), a synthase derived nitric oxide (NO) in the central nervous system. Here, we found that the excessive expression of nNOS and thereby the high concentration of NO followed by single-prolonged stress (SPS) caused suppression of the activity of DRN 5-HT neurons, inducing PTSD-like phenotype including increased anxiety-like behaviors, enhanced contextual fear memory, and fear generalization. Our study uncovered an important role of DRN nNOSNO pathway in the pathology of PTSD, which may contribute to new understanding of the molecular mechanism of PTSD. (c) 2021 Elsevier Inc. All rights reserved.

Automated summary

This study reveals that excessive expression of nNOS and high concentration of NO after single-prolonged stress (SPS) can suppress the activity of DRN 5-HT neurons, inducing PTSD-like phenotype. This finding sheds light on the role of DRN nNOSNO pathway in the pathology of PTSD and contributes to a new understanding of the molecular mechanism of PTSD.