Putative involvement of the nitrergic system on the consolidation, but not initiation, of behavioral sensitization after conspecific alarm substance in zebrafish

Abstract

Stressful manipulations can sensitize the behavior of an organism, increasing anxiety-like behavior after a delay; this long-term stress sensitization can represent the pathophysiological basis of trauma- and stress-related disorders (TRSDs), of which the most prevalent is post-traumatic stress disorder (PTSD). A role for the glutamate-nitric oxide pathway in this sensitization is implied by behavioral, neurophysiological and genomic data on different species. Here, we report on the long-term sensitization of anxiety-like behavior in zebrafish and the possible participation of nitric oxide in this process. Zebrafish exposed to a conspecific alarm substance (AS) show increased anxiety-like behavior at least 24h after stimulus delivery. Blocking nitric oxide synthesis with l-NAME (5mg/kg) 30min, but not 90min, after AS exposure blocks the sensitization of scototaxis and risk assessment, while treatment 90min after exposure blocks the sensitization of thigmotaxis and erratic swimming; l-NAME was not effective when administered 30min before AS exposure. These data suggest a participation of nitric oxide in the consolidation, but not in the initiation, of behavioral sensitization after predator threat.

Sensory ecology of ostariophysan alarm substances

“…Moreover, CAS also serves as a platform for learning, as animals learn to avoid areas or cues which were previously associated with schreckstoff exposure (Hall & Suboski, , 1995b; Maximino et al ., ; Ruhl et al ., ). Finally, as appears to be the case with predator odours in rodents (Blanchard et al ., ), CAS can also produce long‐term (time‐dependent) sensitization of defensive responses (Lima et al ., , ), suggesting a basis for the creation of models for post‐traumatic stress disorder (Section 10).…”

“…In D. rerio , the use of prolonged exposure to a predator has been proposed as a model for PTSD (Stewart, Braubach, et al ., ); while this setup produces protracted predator avoidance, it is not able to model situations in which the traumatic event is brief, a requirement for adequate models for PTSD (Yehuda & Antelman, ). We have exploited CAS as a stimulus to induce a PTSD‐like syndrome in D. rerio (Lima et al ., , ). PTSD produced anxiety‐like behaviour that is qualitatively and quantitatively different 24 h after exposure than immediately after exposure, suggesting that the stress‐free period leads to incubation of stress–fear responses instead of merely producing a sustained response (Lima et al ., ).…”

“…Finally, this time-dependent sensitization does not affect all animals equally, with about one-quarter of the animals showing maladaptive responses and another quarter displaying resilience (Lima et al, 2016). Currently, the model is being used to evaluate the role of nitric oxide on PTSD (see also Lima et al, 2015).…”

NOS-2 Participates in the Behavioral Effects of Ethanol Withdrawal in Zebrafish

“…Chronic ethanol exposure also produces oxidative stress, but not increased nitrite, in the zebrafish brain [23], suggesting that the effect on the nitrergic pathway is specific to withdrawal. Both oxidative stress [24,25] and nitric oxide [26,27] have been implicated in stress-induced anxiogenesis in zebrafish, suggesting that the nitrergic system is a common mediator of the behavioral effects of stressors. EtOH-WD has also been shown, in rodents, to sensitize neurons associated with defensive behavior [28,29].…”

NOS-2 Participates in the Behavioral Effects of Ethanol Withdrawal in Zebrafish

“…Chronic ethanol exposure also produces oxidative stress, but not increased nitrite, in the zebrafish brain [28], suggesting that the effect on the nitrergic pathway is specific to withdrawal. Both oxidative stress [29,30] and nitric oxide [31,32] have been implicated in stress-induced anxiogenesis in zebrafish, suggesting that the nitrergic system is a common mediator of the behavioral effects of stressors. EtOH-WD has also been shown, in rodents, to sensitize neurons associated with defensive behavior [33,34].…”