Neuroscience researchers that wish to address compelling questions in psychopharmacology would benefit from the use of zebrafish, which have a behavioral repertoire that is rich and complex and that reflects many fundamental processes in humans, such as those that evoke anxiety. Zebrafish behavior is easily quantified in diverse test environments, but it is important to consider the conditions used to house the fish, prior to the behavioral testing, when designing experiments. Studies show that fish housed at high densities exhibit elevated cortisol levels as compared with fish housed at lower densities. The literature is less clear about the behavioral consequences of housing and handling. We examined the effects of housing (group versus paired) on several behavioral parameters. We observed that group-housed fish exhibited an anxious phenotype as evidenced by tank diving and meandering. Other more general indicators of movement and spatial navigation were unaffected by housing. This study focused on two specific housing environments, and the results support the need for continued research in this area to further elucidate the contributions of housing and handling on the subtleties of zebrafish behavioral markers.

Anesthetics evoke a stress-response, upregulating heat shock genes. This neuroprotective response to proteotoxic stress represents preconditioning, a process by which neuronal tissue, previously exposed to anesthetics, is protected against future insult. It presumes a sub-lethal injury, affecting protein unfolding. Our hypothesis is: preconditioning evokes molecular events that result in downstream changes that offer a selective advantage in terms of neuronal function. We focused on the neurobehavioral aspects which we neurophenotyped. Larval zebrafish were exposed to trifluoroethanol (TFE), an anesthetic mimetic, and tested for both individual and group behavioral markers of neuronal function. In bright/dark tests, we observed that TFE-exposed larvae spent more time in the dark area (typically an adult-like response) than control larvae. The response of TFE larvae to noise startle was directly opposite to that of controls. TFE larvae swam towards the source of the startle (into the bright zone), whereas control larvae swam away from the source of the startle (into the dark), typical of fear-response. The larvae also exhibited several differences in social behaviors, including synchronized schooling and shoaling behaviors. The TFE-group showed a greater number of synchronized events versus controls. The TFE-group also exhibited more shoaling events compared with controls. While the long-term effects have yet to be determined, these results shed light on the mechanism of anesthetic preconditioning. These complex zebrafish behaviors normally develop with age and therefore represent, in the TFE-exposed group, a pattern of accelerated maturation of neuronal function, which is the neurophenotype attributed to preconditioning.

Permanent post-operative cognitive dysfunction (POCD) is a grim outcome to an estimated 6% of elderly surgical patients. Volatile anesthetics impact neuronal tissue independent of effects attributed to the physical trauma of the surgery itself. While it is recognized that all aspects related to surgery may contribute to cognitive loss in some manner, the present paper focuses on the role of volatile anesthetics in promoting POCD. There is an increased risk of onset and progression of Alzheimer's disease (AD) from POCD, implying that the neuropathogenesis between the two is similar. Human studies, being ethically limited in scope, require animal models as a substitute. While the literature using rodent models contains valuable information, we believe that the accessible and practical zebrafish will greatly enhance our further understanding of the molecular mechanism of POCD as it relates to AD. Disease genes and fundamental neurobehaviors of these teleost fish mirror those of mammals and humans, validating their use as a core research model for AD. Since the gradual senescence seen in zebrafish also resembles that found in humans, we numerically correlated the two lifespans, offering researchers a computational tool. Zebrafish, being aquatic animals, necessitates the use of miscible compounds, such as trifluoroethanol, whose anesthetic potency we are presenting. We also review the rodent and zebrafish literature relevant to POCD. Continued research with the leading-edge zebrafish unlocks the possibility that, in the future, perioperative intervention will prevent POCD.

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