Nitrergic Signaling Mediation of Neurobehavioral Responses to Stress in Zebrafish.

Nitric oxide (NO) is a gaseous transmitter that is involved in the regulation of multiple behavioral processes in the brain. Here, we review the participation of this molecule in zebrafish neurobehavioral responses to stress. NO signaling pathways are considerably conserved in this species, and different pathways appear to be related to the complex regulation of behavior by this molecule. NO acts as a downstream integrator of responses to different upstream signals, including glutamate, serotonin, and inflammatory mediators; as a result, it participates in both anxiolytic and anxiogenic effects of drugs acting at different targets. There is considerable evidence for the participation of both a glutamate/NOS-1 pathway and a KCNN/NOS-2 pathway in long-term behavioral sensitization to stress in zebrafish, suggesting that this molecule regulates metaplasticity in circuits that mediate defensive responses. Important questions remain unanswered, including the relationship between NO signaling, oxidative stress, and neuroinflammation, as well as the actual mechanisms of metaplasticity in the zebrafish brain.