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Event: 2308

Key Event Title

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

Increased, stimulation of brain serotonin 5-HT1a, 5-HT2c receptors

Short name

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Biological Context

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Level of Biological Organization
Organ

Organ 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

Organ term
brain

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
serotonin receptor activity	Surface of brain	increased
serotonin receptor signaling pathway	5-hydroxytryptamine receptor 1A	increased
serotonin receptor signaling pathway	5-hydroxytryptamine receptor 2C	increased

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	OECD Status
Inhibition, 5-hydroxytryptamine transporter (5-HTT; SERT) leads to Inhibition, Feeding	KeyEvent	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
fish	fish	Moderate	NCBI
rodents	rodents	Moderate	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

Serotonin (5-HT) is a neurotransmitter which stimulates pathways resulting in a variety of downstream behavior effects (McDonald 2017; Ramsteijn et al. 2020). Activation of different pathways is mediated by different receptors located in different tissue types, with serotonin receptors classified into 7 families and 14 receptor subtypes (McDonald 2017; Barnes et al. 2021). Increased levels of serotonin result in increased stimulation of serotonin 5-HT1a, 5-HT2c receptors located in brain tissue. In the brain, 5-HT1a receptors have been found in the septum, thalamus, hippocampus, entorhinal cortex, interpeduncular nucleus, olfactory bulb, amygdala, hypothalamic subnuclei, and subareas of the cortex and raphe nuclei (Barnes et al. 2021). In the brain, 5-HT2c receptors have been found in choroid plexus, the basal ganglia, limbic system, and prefrontal cortex (Barnes et al. 2021).

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

Stimulation of brain 5-HT1a, 5-HT2c receptors have been studied by a variety of techniques including radiolabeled compounds, receptor binding, real time PCR, in situ hybridization, Western and Northern blotting, and immunohistochemistry (Barnes et al. 2021). Stimulation of brain 5-HT1a, 5-HT2c receptors by serotonin (5-HT) is often measured indirectly by use of antagonist compounds to block activation of receptors (methysergide for 5-HT1/5-HT2 in Ortega et al. 2013, 8-OH-DPAT for 5-HT1a in Perez-Maceira et al. 2014 and Perez-Maceria et al. 2016; MK212 for 5-HT2c in Perez-Maceira et al. 2014 and Perez-Maceria et al. 2016; WAY 161503 for 5-HT2c in Perez-Maceria et al. 2016; overview of compounds in Barnes et al. 2021).

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. Plausible to be applicable in a wide variety of invertebrate and vertebrate taxa due to functional conservation of serotonin pathways (Bacque-Cazenave et al. 2020).

References

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

Bacque-Cazenave, J., Bharatiya, R., Barriere, G., Delbecque, J.-P., Bouguiyoud, N., Di Giovanni, G., Cattaert, D., and De Deurwaerdere, P. 2020. Serotonin in Animal Cognition and Behavior. International Journal of Molecular Sciences 21(5): 1649.

Barnes, N.M., Ahern, G.P., Becamel, C., Bockaert, J., Camilleri, M., Chaumont-Dubel, S., Claeysen, S., Cunningham, K.A., Fone, K.C., Gershon, M., Di Giovanni, G., Goodfellow, N.M., Halberstadt, A.L., Hartley, R.M., Hassaine, G., Herrick-Davis, K., Hovius, R., Lacivita, E., Lambe, E..K, Leopoldo, M., Levy, F.O., Lummis, S.C.R, Marin, P., Maroteaux, L., McCreary, A.C., Nelson, D.L., Neumaier, J.F., Newman-Tancredi, A., Nury, H., Roberts, A., Roth, B.L., Roumier, A., Sanger, G.J., Teitler, M., Sharp, T., Villalon, C.M., Vogel, H., Watts, S.W., and Hoyer, D. 2021. International Union of Basic and Clinical Pharmacology. CX. Classification of Receptors for 5-hydroxytryptamine; Pharmacology and Function. Pharmacological Reviews 73(1): 310-520.

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.

Ortega, V.A., Lovejoy, D.A., and Bernier, N.J. 2013. Appetite-suppressing effects and interactions of centrally administered corticotropin-releasing factor, urotensin I and serotonin in rainbow trout (Oncorhynchus mykiss). Frontiers in Neuroscience 7: 196.

Perez-Maceira, J.J., Mancebo, M.J., and Aldegunde, M. 2014. The involvement of 5-HT-like receptors in the regulation of food intake in rainbow trout (Oncorhynchus mykiss). Comparative Biochemistry and Physiology, Part C-Toxicology and Pharmacology 161: 1–6.

Perez-Maceira, J.J., Otero-Rodino, C., Mancebo, M.J., Soengas, J.L., and Aldegunde, M. 2016. Food intake inhibition in rainbow trout induced by activation of serotonin 5‑HT2C receptors is associated with increases in POMC, CART and CRF mRNA abundance in hypothalamus. Comparative Biochemistry and Physiology, Part B-Biochemical Systems and Environmental Physiology 186(3): 313-321.

Ramsteijn A.S., Van de Wijer, L., Rando, J., van Luijk, J., Homberg, J.R., and Olivier, J.D.A. 2020. Perinatal selective serotonin reuptake inhibitor exposure and behavioral outcomes: A systematic review and meta-analyses of animal studies. Neuroscience and Biobehavior Reviews 114: 53–69.

NOTE: Italics symbolize edits from John Frisch January 2025.