Serotonin in Panic and Anxiety Disorders

Guimarães, Francisco Silveira; Zangrossi, Hélio; Ben, Cristina Marta Del; Graeff, Frederico Guilherme

doi:10.1016/s1569-7339(10)70105-3

Cited by 8 publications

(5 citation statements)

References 151 publications

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“…These results are in line with clinical data (Mortimore & Anderson, 2000;Graeff et al, 2001;Garcia-leal et al, 2014), as well as preclinical data on mammals (Pinheiro et al, 2007;Guimarães et al, 2010;Paul et al, 2014;Graeff, 2016). The participation of this monoamine in behavioural and neuroendocrine responses to stressors appears to be different, however.…”

Section: Monoaminergic Innervation In Teleostssupporting

confidence: 88%

The Integration of Sociality, Monoamines, and Stress Neuroendocrinology in Fish Models: Applications in the Neurosciences

Soares¹,

Maximino²

2018

Preprint

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Animal-focused research has been crucial for scientific advancement however, in this matter, rodents are still taking a starring role. Coming out from merely being supportive of evidence found in rodents, the use of fish models has slowly taken a more central role and expanded its overall contributions in areas such as social sciences, evolution, physiology, and recently in translational medical research. In neurosciences, zebrafish has been widely adopted, contributing to our understanding of the genetic control of brain processes, and the effects of pharmacological manipulations. However, discussion continues regarding the paradox of function versus structure, when fish and mammals are compared, and on the potentially evolutionarily conserved nature of behaviour across fish species. From the behavioural stand point we explorted aversive/stress and social behaviour in selected fish models, and refer to the extensive contributions of stress and monoaminergic systems. We suggest that, in spite of marked neuroanatomical differences between fish and mammals, stress and sociality are conserved at the behavioural and molecular levels. We also suggest that stress and sociality are mediated by monoamines in predictable and non-trivial ways, and that monoamines could “bridge” the relationship between stress and social behaviour. To reconcile the level of divergence with the level of similarity, neuroanatomy, pharmacology, behavioural analysis, and ecology studies conducted in the laboratory and in nature need to add to each other and enhance our understanding of fish behaviour and ultimately how this all may translate to better model systems for translational studies.

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Section: Monoaminergic Innervation In Teleostssupporting

confidence: 88%

The Integration of Sociality, Monoamines, and Stress Neuroendocrinology in Fish Models: Applications in the Neurosciences

Soares¹,

Maximino²

2018

Preprint

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“…Phasic serotonin has been proposed to modulate fear‐like behavior in mammals before (Guimarães, Zangrossi, Del‐Ben, & Graeff, ; Paul et al, ; Zangrossi et al, ); the Deakin/Graeff theory suggests a “panic inhibition system” (Paul et al, ; Silva, Rocha, Herculano, Lima‐Maximino, & Maximino, ) that inhibits behavioral and sympathoexcitatory responses to these stimuli, and is mediated by serotonergic signaling. The theory proposes a “dual role” for serotonin, increasing anxiety‐like responses and inhibiting fear‐like responses.…”

Section: Discussionmentioning

confidence: 99%

Phasic and tonic serotonin modulate alarm reactions and post‐exposure behavior in zebrafish

Lima-Maximino

Pyterson

Silva

et al. 2020

Journal of Neurochemistry

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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.

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“…Phasic serotonin has been proposed to modulate fear-like behavior in mammals before (Zangrossi Jr et al 2001;Paul et al 2014;Guimarães et al 2010); the Deakin/Graeff theory suggests a "panic inhibition system" (Paul et al 2014;Silva et al 2019) that inhibits behavioral and sympathoexcitatory responses to these stimuli, and is mediated by serotonergic signaling. The theory proposes a "dual role" for serotonin, increasing anxiety-like responses and inhibiting fearlike responses.…”

Section: Behavior During and After Cas Exposurementioning

confidence: 99%

Phasic and tonic serotonin modulate alarm reactions and post-exposure behavior in zebrafish

Lima-Maximino

Pyterson

Silva

et al. 2019

Preprint

View full text Add to dashboard Cite

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,

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Serotonin in Panic and Anxiety Disorders

Cited by 8 publications

References 151 publications

The Integration of Sociality, Monoamines, and Stress Neuroendocrinology in Fish Models: Applications in the Neurosciences

The Integration of Sociality, Monoamines, and Stress Neuroendocrinology in Fish Models: Applications in the Neurosciences

Phasic and tonic serotonin modulate alarm reactions and post‐exposure behavior in zebrafish

Phasic and tonic serotonin modulate alarm reactions and post-exposure behavior in zebrafish

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