PUBLICATION
Agouti-induced anxiety-like behaviour is mediated by central serotonergic pathways in zebrafish
- Authors
- Godino-Gimeno, A., Rocha, A., Chivite, M., Saera-Vila, A., Rotllant, J., Míguez, J.M., Cerdá-Reverter, J.M.
- ID
- ZDB-PUB-240709-16
- Date
- 2024
- Source
- The Journal of neuroscience : the official journal of the Society for Neuroscience 44(32): (Journal)
- Registered Authors
- Cerdá-Reverter, José Miguel, Rotllant, Josep
- Keywords
- none
- MeSH Terms
-
- Fluoxetine/pharmacology
- Female
- Animals, Genetically Modified
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- Selective Serotonin Reuptake Inhibitors/pharmacology
- Male
- Anxiety*/metabolism
- Anxiety*/psychology
- Zebrafish*
- Agouti-Related Protein/genetics
- Agouti-Related Protein/metabolism
- Animals
- Behavior, Animal/drug effects
- Behavior, Animal/physiology
- Serotonin*/metabolism
- Dopamine/metabolism
- PubMed
- 38977301 Full text @ J. Neurosci.
Citation
Godino-Gimeno, A., Rocha, A., Chivite, M., Saera-Vila, A., Rotllant, J., Míguez, J.M., Cerdá-Reverter, J.M. (2024) Agouti-induced anxiety-like behaviour is mediated by central serotonergic pathways in zebrafish. The Journal of neuroscience : the official journal of the Society for Neuroscience. 44(32):.
Abstract
Overexpression of the agouti-signalling protein (asip1), an endogenous melanocortin antagonist, under the control of a constitutive promoter in zebrafish [Tg(Xla.Eef1a1:Cau.Asip1]iim4] (asip1-Tg) increases food intake by reducing sensitivity of the central satiety systems and abolish circadian activity rhythms. The phenotype also shows increased linear growth and body weight, yet no enhanced aggressiveness in dyadic fights is observed. In fact, asip1-Tg animals choose to flee to safer areas rather than face a potential threat thus suggesting a potential anxiety-like behaviour (ALB). Standard behavioural tests, i.e. the open field test (OFT), the novel object test (NOT) and the novel tank dive test (NTDT) were used to investigate thigmotaxis and ALB in male and female zebrafish. Results showed that the asip1-Tg strain exhibited severe ALB in every test, mainly characterised by pronounced freezing behaviour and increased linear and angular swimming velocities. asip1-Tg animals exhibited low central serotonin (5HT) and dopamine (DA) levels and high turnover rates, thus suggesting that central monoaminergic pathways might mediate melanocortin antagonist-induced ALB. Accordingly, the treatment of asip1-Tg animals with fluoxetine, a selective serotonin reuptake inhibitor (SSRI), reversed the ALB phenotype in NTDT as well as 5-HT turnover. Genomic and anatomical data further supported neuronal interaction between melanocortinergic and serotonergic systems. These results suggest that inhibition of the melanocortin system by ubiquitous overexpression of endogenous antagonist has an anxiogenic effect mediated by serotonergic transmission.Significance statement In this paper, we show that inhibition of the melanocortin system by ubiquitous overexpression of endogenous antagonists has a potent anxiogenic effect mediated by serotonergic transmission in zebrafish. asip1-overexpressing fish (asip1-Tg) also exhibit a severe disruption of the central satiety system, leading to increased feed intake and abolishing circadian locomotor activity patterns. The melanocortin system plays a key role in the control of hunger, and data suggest that the anxiety-like behaviour in asip1-Tg may be related to the feeding anxiety induced by negative energy balance states, which promote constant foraging and thus disrupt activity rhythms. This makes asip1-Tg animals an excellent model to study dieting-induced anxiety, one of the major causes of dieting failure.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping