PUBLICATION

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

Authors
do Carmo Silva, R.X., do Nascimento, B.G., Gomes, G.C.V., da Silva, N.A.H., Pinheiro, J.S., da Silva Chaves, S.N., Pimentel, A.F.N., Costa, B.P.D., Herculano, A.M., Lima-Maximino, M., Maximino, C.
ID
ZDB-PUB-210924-6
Date
2021
Source
Pharmacology, biochemistry, and behavior   210: 173276 (Journal)
Registered Authors
Maximino, Caio
Keywords
5-HT2C receptors, Anxiety, Fear, Responses to threat, Zebrafish
MeSH Terms
  • Animals
  • Anxiety/drug therapy
  • Anxiety/metabolism
  • Behavior, Animal/drug effects*
  • Escape Reaction/drug effects*
  • Fear/drug effects*
  • Receptor, Serotonin, 5-HT2C/metabolism
  • Receptors, Serotonin/metabolism
  • Serotonin/metabolism
  • Serotonin 5-HT2 Receptor Agonists/pharmacology*
  • Serotonin 5-HT2 Receptor Antagonists/pharmacology*
  • Zebrafish
PubMed
34555392 Full text @ Pharmacol. Biochem. Behav.
Abstract
Serotonin (5-HT) receptors have been implicated in responses to aversive stimuli in mammals and fish, but its precise role is still unknown. Moreover, since at least seven families of 5-HT receptors exist in vertebrates, the role of specific receptors is still debated. Aversive stimuli can be classified as indicators of proximal, distal, or potential threat, initiating responses that are appropriate for each of these threat levels. Responses to potential threat usually involve cautious exploration and increased alertness, while responses to distal and proximal threat involve a fight-flight-freeze reaction. We exposed adult zebrafish to a conspecific alarm substance (CAS) and observed behavior during (distal threat) and after (potential threat) exposure, and treated with the 5-HT2C receptor agonists MK-212 or WAY-161503 or with the antagonist RS-102221. The agonists blocked CAS-elicited defensive behavior (distal threat), but not post-exposure increases in defensive behavior (potential threat), suggesting inhibition of responses to distal threat. MK-212 blocked changes in freezing elicited by acute restraint stress, a model of proximal threat, while RS-102221 blocked changes in geotaxis elicited this stressor. We also found that RS-102221, a 5-HT2C receptor antagonist, produced small effect on behavior during and after exposure to CAS. Preprint: https://www.biorxiv.org/content/10.1101/2020.10.04.324202; Data and scripts: https://github.com/lanec-unifesspa/5-HT-CAS/tree/master/data/5HT2C.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping