Current models in biological psychiatry focus on a handful of model species, and the majority of work relies on data generated in rodents. However, in the same sense that a comparative approach to neuroanatomy allows for the identification of patterns of brain organization, the inclusion of other species and an adoption of comparative viewpoints in behavioral neuroscience could also lead to increases in knowledge relevant to biological psychiatry. Specifically, this approach could help to identify conserved features of brain structure and behavior, as well as to understand how variation in gene expression or developmental trajectories relates to variation in brain and behavior pertinent to psychiatric disorders. To achieve this goal, the current focus on mammalian species must be expanded to include other species, including non-mammalian taxa. In this article, we review behavioral neuroscientific experiments in non-mammalian species, including traditional “model organisms” (zebrafish and Drosophila) as well as in other species which can be used as “reference.” The application of these domains in biological psychiatry and their translational relevance is considered.

Current theories on the role of serotonin (5-HT) in vertebrate defensive behavior suggest that this monoamine increases anxiety but decreases fear, by acting at different levels of the neuroaxis. This paradoxical, dual role of 5-HT suggests that a serotonergic tone inhibits fear responses, while an acute increase in 5-HT would produce anxiety-like behavior. However, so far no evidence for a serotonergic tone has been found. Using zebrafish alarm responses, we investigate the participation of phasic and tonic 5-HT levels in fear-like behavior, as well as in behavior after stimulation.Conspecific alarm substance (CAS) increased bottom-dwelling and erratic swimming, and animals transferred to a novel environment after CAS exposure (post-exposure behavior) showed increased bottom-dwelling and freezing. Clonazepam blocked CAS effects during and after exposure. Acute fluoxetine dose-dependently decreased fear-like behavior, but increased post-exposure freezing. Metergoline had no effect on fear-like behavior, but blocked the effects of CAS on post-exposure behavior; similar effects were observed with para-chlorophenylalanine. Finally, CAS was shown to decrease the activity of monoamine oxidase in the zebrafish brain after exposure.These results suggest that phasic and tonic serotonin encode an aversive expectation value, switching behavior toward cautious exploration/risk assessment/anxiety when the aversive stimulus is no longer present. K E Y W O R D Salarm substance, fear, panic, serotonin, zebrafish | INTRODUC TI ONThe neurocircuitry of defensive reactions involves regulation by a plethora of neuromodulators, including monoamines and peptides (Maximino, 2012). In vertebrates, the monoamine serotonin (5-HT) is produced in specific brain nuclei, including the raphe, and is thought to inhibit fear/escape responses to proximate threat by acting on more caudal structures of the aversive brain system (Deakin & Graeff, 1991; S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section. How to cite this article: Lima-Maximino M, Pyterson MP, do Carmo Silva RX, et al. Phasic and tonic serotonin modulate alarm reactions and post-exposure behavior in zebrafish. J. Neurochem. 2020;153:495-509.https://doi.

Current theories on the role of serotonin (5-HT) in vertebrate defensive behavior suggest that this monoamine increases anxiety but decreases fear, by acting at different levels of the neuroaxis. This paradoxical, dual role of 5-HT suggests that a serotonergic tone inhibits fear responses, while an acute increase in 5-HT would produce anxiety-like behavior. However, so far no evidence for a serotonergic tone has been found. Using zebrafish alarm responses, we investigate the participation of phasic and tonic 5-HT levels in fear-like behavior, as well as in behavior after stimulation.Conspecific alarm substance (CAS) increased bottom-dwelling and erratic swimming, and animals transferred to a novel environment after CAS exposure (post-exposure behavior) showed increased bottom-dwelling and freezing. Clonazepam blocked CAS effects during and after exposure. Acute fluoxetine dose-dependently decreased fear-like behavior, but increased post-exposure freezing.Metergoline had no effect on fear-like behavior, but blocked the effects of CAS on post-exposure behavior; similar effects were observed with pCPA. Finally, CAS was shown to decrease the activity of monoamine oxidase in the zebrafish brain after exposure. These results suggest that phasic and tonic serotonin encode an aversive expectation value, switching behavior towards cautious exploration/risk assessment/anxiety when the aversive stimulus is no longer present. zebrafish, 5-HT 1A and 5-HT 1B receptor antagonists decrease anxiety-like behavior (Maximino et al. ,635 was not able to alter anxiety-like behavior after exposure, the drug blocked the increased geotaxis during CAS exposure, both in the first minutes of exposure and in the last minutes (Nathan et al. 2015). Blocking 5-HT 2 -type receptors with methysergide did not affect these responses,