Elsevier

Behavioural Brain Research

Volume 256, 1 November 2013, Pages 328-345
Behavioural Brain Research

Review
Animal models of the serotonin syndrome: A systematic review

https://doi.org/10.1016/j.bbr.2013.08.045Get rights and content
Under a Creative Commons license
open access

Highlights

  • There is no consistent procedure to model the serotonin syndrome (SS) in rodents.

  • Provide a comprehensive review of rodent models of the SS.

  • Analyzed behavioral and autonomic responses induced by serotonergic drugs.

  • Standardized test methods will improve future studies using animal models of the SS.

Abstract

The serotonin syndrome (SS) is a potentially life-threatening disorder in humans which is induced by ingestion of an overdose or by combination of two or more serotonin (5-HT)-enhancing drugs. In animals, acute administration of direct and indirect 5-HT agonists also leads to a set of behavioral and autonomic responses. In the current review, we provide an overview of the existing versions of the animal model of the SS. With a focus on studies in rats and mice, we analyze the frequency of behavioral and autonomic responses following administration of 5-HT-enhancing drugs and direct 5-HT agonists administered alone or in combination, and we briefly discuss the receptor mediation of these responses. Considering species differences, we identify a distinct set of behavioral and autonomic responses that are consistently observed following administration of direct and indirect 5-HT agonists. Finally, we discuss the importance of a standardized assessment of SS responses in rodents and the utility of animal models of the SS in translational studies, and provide suggestions for future research.

Abbreviations

5-HT
serotonin
5-HTP
5-hydroxy-l-tryptophan
5-HTT
5-HT transporter
MAO
monoamine oxidase
MAOA-I
monoamine oxidase type A inhibitor
MAOB-I
monoamine oxidase type A inhibitor
MAOA/B-I
monoamine oxidase type A/B inhibitor
SNRI
serotonin/norepinephrine reuptake inhibitor
SS
serotonin syndrome
SRI
serotonin reuptake inhibitor
SSRI
selective serotonin reuptake inhibitor
TCA
tricyclic antidepressant

Keywords

5-HT-enhancing drug
5-HT agonist
Animal model
Core response
Mouse
Rat
Serotonin
Serotonin syndrome
Validity

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