5-HT2C agonists and antagonists block different components of behavioral responses to potential, distal, and proximal threat in zebrafish

Silva, Rhayra Xavier do Carmo; Nascimento, Bianca Gomes do; Gomes, Gabriela Cristini Vidal; Silva, Nadyme Assad Holanda da; Pinheiro, Jéssica Souza; Chaves, Suianny Nayara da Silva; Pimentel, Ana Flávia Nogueira; Costa, Bruna Patrícia Dutra; Herculano, Anderson Manoel; Lima-Maximino, Monica Gomes; Maximino, Caio

doi:10.1016/j.pbb.2021.173276

Cited by 5 publications

(3 citation statements)

References 64 publications

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“…Animals were treated either with vehicle (10% DMSO), the 5-HT 2C receptor agonist MK-212 (6-chloro-2-(1-piperazinyl)pyrazine), CPP; CAS Number 64022-27-1; 2 mg/kg, a dose shown to block alarm reactions in zebrafish (do Carmo Silva et al, 2021)), or the 5-HT 2C receptor antagonist RS-102221 (8-[5-(2,4-Dimethoxy-5-(4-trifluoromethylphenylsulphonamido)phenyl-5-oxopentyl]-1,3,8-triazaspiro[4.5]decane-2,4-dione; CAS Number 185376-97-0; 2 mg/kg, a dose shown to block post-alarm substance anxiety-like behavior in zebrafish (do Carmo Silva et al, 2021)). Experimenters were blind to drug treatment by coding vials, and animals were randomly assigned to treatment groups through the use of random numbers (http://jerrydallal.com/random/assign.htm).…”

Section: Methodsmentioning

confidence: 99%

Roles of the 5-HT2C receptor on zebrafish sociality

Moura

Pyterson

Pimentel

et al. 2022

Preprint

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Serotonin (5-HT) receptors have been implicated in social behavior in vertebrates. Zebrafish (Danio rerio) have been increasingly being used behavioral neuroscience to study the neurobiological correlates of behavior, including sociality. Nonetheless, the role of 5-HT2C receptors in different social functions were not yet studied in this species. Zebrafish were treated with the agonist MK-212 (2 mg/kg) or the antagonist RS-102221 (2 mg/kg) and tested in the social interaction and social novelty tests, conditional approach test, or mirror-induced aggressive displays. MK-212 increased preference for an unknown conspecific in the social investigation test, but also increased preference for the known conspecific in the social novelty test; RS-102221, on the other hand, decreased preference in the social investigation test but increased preference for the novel conspecific in the social novelty test. MK-212 also decreased predator inspection in the conditional approach test. While RS-102221 decreased time in the display zone in the mirror-induced aggressive display test, it increased display duration. Overall, these results demonstrate the complex role of 5-HT2C receptors in different social contexts in zebrafish, revealing a participation in social plasticity in vertebrates.

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Section: Methodsmentioning

confidence: 99%

Roles of the 5-HT2C receptor on zebrafish sociality

Moura

Pyterson

Pimentel

et al. 2022

Preprint

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“…Given the role of the serotonergic system in regulating and mediating responses to threat, and the recently uncovered role of 5-HT 2 receptors in the types of responses to proximal threat which are modulated by social defeat stress (Silva et al, 2021) as well as its complex roles in sociality (Ponzoni et al, 2016;Moura et al, 2023), the aim of the present work was to elucidate the participation of 5-HT 2C receptors on social rank-modulated differences in responses to a potential threat. In order to do that, animals were separated in pairs, and allowed to interact for five days; after that, the dominant-subordinate rank was determined, and animals were treated with a 5-HT 2C receptor agonist (MK-212) or antagonist (RS-102221) before being observed in the novel tank test, an widely-used test to assay responses to potential threat/anxiety-like behavior (Bencan et al, 2009;Cachat et al, 2011;Levin et al, 2007).…”

Section: /19mentioning

confidence: 99%

“…have also been shown to result in increased geotaxis, freezing, and erratic swimming in stressed individuals (Ghisleni et al, 2012;Lima-Maximino et al, 2020;Silva et al, 2021). Increased freezing behavior in subordinates can also been associated with a reactive or passive coping style, which is typical of subordinate individuals.…”

Section: /19mentioning

confidence: 99%

Social status in zebrafish modulates the behavioral response to 5-HT2C receptor agonists and antagonists

Oliveira

Alves

Soares

et al. 2023

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The effects of previous social experiences on social behavior have been demonstrated across species both in cooperative and competitive contexts. In dominance-subordinate hierarchies, differences across social ranks have been observed in many different mechanisms. Dominance hierarchies interfere in defensive behavior, where subordinate animals present a greater defensive behavior, regarding potential threats ("anxiety-like behavior"), than dominant animals. The serotonergic system plays a key role in regulating and mediating threat responses, including 5-HT2 receptors in the types of proximal threat responses modulated by the stress of social defeat. We separated 148 adult zebrafish in pairs, and allowed to interact for five days; after that, the dominant-subordinate rank was determined, and animals were treated with a 5-HT2C receptor agonist (MK-212) or antagonist (RS-102221) before being observed in the novel tank test. While MK-212 increased bottom-dwelling, erratic swimming, and freezing across all statuses, RS-102221 decreased these variables in dominants but increased them in subordinates. Moreover, the effects of MK-212 were larger in subordinates than in controls or dominants, suggesting a sensitization of the 5-HT2C receptor.

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