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Event: 619

Key Event Title

A descriptive phrase which defines a discrete biological change that can be measured. More help

Inhibition, 5-hydroxytryptamine transporter (5-HTT; SERT)

Short name

The KE short name should be a reasonable abbreviation of the KE title and is used in labelling this object throughout the AOP-Wiki. More help

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Biological Context

Structured terms, selected from a drop-down menu, are used to identify the level of biological organization for each KE. More help

Level of Biological Organization
Molecular

Cell term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place. For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable. For individual/population events, the organ context is not applicable. Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Cell term
motor neuron

Organ term

Key Event Components

The KE, as defined by a set structured ontology terms consisting of a biological process, object, and action with each term originating from one of 14 biological ontologies (Ives, et al., 2017; https://aopwiki.org/info_pages/2/info_linked_pages/7#List). Biological process describes dynamics of the underlying biological system (e.g., receptor signalling).Biological process describes dynamics of the underlying biological system (e.g., receptor signaling). The biological object is the subject of the perturbation (e.g., a specific biological receptor that is activated or inhibited). Action represents the direction of perturbation of this system (generally increased or decreased; e.g., ‘decreased’ in the case of a receptor that is inhibited to indicate a decrease in the signaling by that receptor). Note that when editing Event Components, clicking an existing Event Component from the Suggestions menu will autopopulate these fields, along with their source ID and description. To clear any fields before submitting the event component, use the 'Clear process,' 'Clear object,' or 'Clear action' buttons. If a desired term does not exist, a new term request may be made via Term Requests. Event components may not be edited; to edit an event component, remove the existing event component and create a new one using the terms that you wish to add. Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Process	Object	Action
neurotransmitter reuptake	sodium-dependent serotonin transporter	decreased
serotonin uptake	sodium-dependent serotonin transporter	decreased

Key Event Overview

AOPs Including This Key Event

All of the AOPs that are linked to this KE will automatically be listed in this subsection. This table can be particularly useful for derivation of AOP networks including the KE.Clicking on the name of the AOP will bring you to the individual page for that AOP. More help

AOP Name	Role of event in AOP	Point of Contact	Author Status
5-HTT block to population decline	MolecularInitiatingEvent	Kellie Fay (send email)	Under Development: Contributions and Comments Welcome
5-HTT block to incr. predation	MolecularInitiatingEvent	Ksenia Groh (send email)	Under Development: Contributions and Comments Welcome
5-HTT leading to population increase	MolecularInitiatingEvent	Kellie Fay (send email)	Under Development: Contributions and Comments Welcome
5-HTT leading to population decline	MolecularInitiatingEvent	Kellie Fay (send email)	Under Development: Contributions and Comments Welcome
5-HTT inhibition leading to population increase	MolecularInitiatingEvent	Kellie Fay (send email)	Under Development: Contributions and Comments Welcome
Inhibition, 5-hydroxytryptamine transporter (5-HTT; SERT) leads to Inhibition, Feeding	MolecularInitiatingEvent	John Frisch (send email)	Under development: Not open for comment. Do not cite

Taxonomic Applicability

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) that help to define the biological applicability domain of the KE.In many cases, individual species identified in these structured fields will be those for which the strongest evidence used in constructing the AOP was available in relation to this KE. More help

Term	Scientific Term	Evidence	Link
rodents	rodents	High	NCBI
fish	fish	High	NCBI

Life Stages

An indication of the the relevant life stage(s) for this KE. More help

Life stage	Evidence
All life stages	Moderate

Sex Applicability

An indication of the the relevant sex for this KE. More help

Term	Evidence
Unspecific	High

Key Event Description

A description of the biological state being observed or measured, the biological compartment in which it is measured, and its general role in the biology should be provided. More help

Inhibitors of the serotonin reuptake transporter (SERT; 5-hydroxytryptamine transporter; 5-HTT) block the reuptake of the neurotransmitter serotonin, increasing its residence time in synapses (McDonald 2017; Correira et al. 2023). Selective serotonin reuptake inhibitor (SSRI) antidepressants are a class of compounds known to inhibit serotonin reuptake transporter activity (McDonald 2017).

How It Is Measured or Detected

A description of the type(s) of measurements that can be employed to evaluate the KE and the relative level of scientific confidence in those measurements.These can range from citation of specific validated test guidelines, citation of specific methods published in the peer reviewed literature, or outlines of a general protocol or approach (e.g., a protein may be measured by ELISA). Do not provide detailed protocols. More help

Toxcast assays that target the serotonin transporter (5-HTT; SERT) gene SLC6A4 include: NVS_TR_rSERT,NVS_TR_rSERT.
SERT activity can be measured by the rate of uptake of radiolabeled compounds into cells, with development of fluorescent dyes a recent development (Persson et al. 2023).
Real time PCR can be used to measure transcript abundance of genes for SERT, which is an indirect – and only semi-quantitative indicator of protein abundance.
Serotonin concentrations can be measured via microdialysis/high-performance liquid chromatography, fast-scan cyclic voltammetry, N-Shaped Multiple Cyclic Square Wave Voltammetry, and Fast-Scan Controlled-Adsorption Voltammetry (Rojas Cabrera et al. 2023).

Domain of Applicability

A description of the scientific basis for the indicated domains of applicability and the WoE calls (if provided). More help

Life Stage: Applies to all life stages with developed brain and central nervous systems.

Sex: Applies to both males and females.

Taxonomic: Primarily studied in laboratory rodents, humans, and fish.

References

List of the literature that was cited for this KE description. More help

Correia, D., Domingues, I., Faria, M., and Oliveira, M. 2023. Effects of fluoxetine on fish: What do we know and where should we focus our efforts in the future? Science of the Total Environment 857: 159486.

McDonald, M.D. 2017. An AOP analysis of selective serotonin reuptake inhibitors (SSRIs) for fish. Comparative Biochemistry and Physiology, Part C-Toxicology and Pharmacology 197: 19–31.

Persson, M., Vikingsson, S., Kronstrand, R., and Green, H. 2023. Characterization of neurotransmitter inhibition for seven cathinones by a proprietary fluorescent dye method. Drug Testing and Analysis 16(4): 339-347.

Rojas Cabrera, J.M., Oesterle, T.S., Rusheen, A.E., Goyal, A., Scheitler, K.M., Mandybur, I., Blaha, C.D., Bennet, K.E., Heien, M.L., Jang, D.P., Lee, K.H., Oh, Y., and Shin, H. 2023. Techniques for Measurement of Serotonin: Implications in Neuropsychiatric Disorders and Advances in Absolute Value Recording Methods. ACS Chemical Neuroscience 14(24): 4264-4273.

NOTE: Italics indicate edits from John Frisch January 2025.