Unpredictable chronic stress decreases inhibitory avoidance learning in Tuebingen Long-Fin zebrafish (Danio rerio Hamilton): stronger effects in the resting phase than in the active phase

Abstract

Zebrafish (Danio rerio Hamilton) are increasingly used as a model to study the effects of chronic stress on brain and behaviour. In rodents, unpredictable chronic stress (UCS) has a stronger effect on physiology and behaviour during the active phase than during the resting phase. Here, we applied UCS during the daytime (active phase) for 7 and 14 days or during the night-time (resting phase) for 7 nights in an in-house-reared Tuebingen long-fin (TLF) zebrafish strain. Following UCS, inhibitory avoidance learning was assessed using a 3 day protocol where fish learn to avoid swimming from a white to a black compartment where they will receive a 3 V shock. Latencies of entering the black compartment were recorded before training (day 1; first shock) and after training on day 2 (second shock) and day 3 (no shock, tissue sampling). Fish whole-body cortisol content and expression levels of genes related to stress, fear and anxiety in the telencephalon were quantified. Following 14 days of UCS during the day, inhibitory avoidance learning decreased (lower latencies on days 2 and 3); minor effects were found following 7 days of UCS. Following 7 nights of UCS, inhibitory avoidance learning decreased (lower latency on day 3). Whole-body cortisol levels showed a steady increase compared with controls (100%) from 7 days of UCS (139%), to 14 days of UCS (174%) to 7 nights of UCS (231%), suggestive of an increasing stress load. Only in the 7 nights of UCS group did expression levels of corticoid receptor genes (mr, grα, grβ) and of bdnf increase. These changes are discussed as adaptive mechanisms to maintain neuronal integrity and prevent overload, and as being indicative of a state of high stress load. Overall, our data suggest that stressors during the resting phase have a stronger impact than during the active phase. Our data warrant further studies on the effect of UCS on stress axis-related genes, especially grβ; in mammals this receptor has been implicated in glucocorticoid resistance and depression.

Peer Review #4 of "Enriched environment prevents oxidative stress in zebrafish submitted to unpredictable chronic stress (v0.1)"

“…We demonstrated for the first time that UCS protocol induced several changes in redox homeostasis in the zebrafish brain and revealed that EE has a protective effect against the oxidative stress induced by the UCS protocol. UCS protocol induces several biochemical changes in the zebrafish brain and through sustained activation of the neuroendocrine axis leads to increased cortisol levels (Piato et al, 2011;Manuel et al, 2014;Marcon et al, 2016;Rambo et al, 2017;Song et al, 2017). This was confirmed by the results recently published in our previous study, which showed that the UCS protocol increased cortisol levels while EE for 21 or 28 days prevented this increase (Marcon et al, 2018).…”

Social Status–Dependent Shift in Neural Circuit Activation Affects Decision Making

“…Zebrafish (Danio rerio) has emerged as a model system in behavioral neuroscience and is used to study social stress (Giacomini et al, 2016), major depressive disorders (Manuel et al, 2014;Fonseka et al, 2016), and aggression (Paull et al, 2010; Oliveira et al, 2011), and their social behaviors have been well described (Dahlbom et al, 2012). When paired, zebrafish interact aggressively with ritualized displays that increase in intensity until a social dominance emerges.…”

Unpredictable Chronic Stress Alters Adenosine Metabolism in Zebrafish Brain

“…Piato and colleagues [17] showed that UCS protocol increased the anxiety and cortisol levels in zebrafish, triggering neuroendocrine disturbances. In addition, UCS promoted an increase of cortisol levels, which could have an important neuromodulatory role in the regulation of neuronal function in the brain, affecting behavior and cognition [6,17]. Studies have demonstrated that corticosteroid hormones interact with various neurotransmitter systems, including purinergic system.…”

“…The shortterm-period stress response is beneficial to an organism because it improves the chances of the individual for survival [5]. However, unpredictable chronic stress (UCS) affects physiological [6,7], immunological [8,9], endocrine [10,11], and developmental processes [12,13]. UCS changes brain physiology and neural circuits [14] and leads to the development of depressive behaviors [15].…”