Agouti-Induced Anxiety-Like Behavior Is Mediated by Central Serotonergic Pathways in Zebrafish.

Autor:	Godino-Gimeno A; Fish NeuroBehaviour Lab, Department of Fish Physiology and Biotechnology, Instituto de Acuicultura de Torre de la Sal, IATS-CSIC, Castellon 12595, Spain., Rocha A; Centro Interdisciplinar de Investigação Marinha e Ambiental (CIIMAR), Terminal de Cruzeiros do Porto de Leixões, Matosinhos 4450-208, Portugal., Chivite M; Centro de Investigación Mariña, Laboratorio de Fisioloxía Animal, Departamento de Bioloxía Funcional e Ciencias da Saúde, Facultade de Bioloxía, Universidade de Vigo, Vigo 36310, Spain., Saera-Vila A; Sequentia Biotech, Barcelona 08018, Spain., Rotllant J; Instituto de Investigaciones Marinas, Consejo Superior de Investigaciones Científicas (IIM-CSIC), Vigo 36208, Spain., Míguez JM; Centro de Investigación Mariña, Laboratorio de Fisioloxía Animal, Departamento de Bioloxía Funcional e Ciencias da Saúde, Facultade de Bioloxía, Universidade de Vigo, Vigo 36310, Spain., Cerdá-Reverter JM; Fish NeuroBehaviour Lab, Department of Fish Physiology and Biotechnology, Instituto de Acuicultura de Torre de la Sal, IATS-CSIC, Castellon 12595, Spain jm.cerda.reverter@csic.es.
Jazyk:	angličtina
Zdroj:	The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] 2024 Aug 07; Vol. 44 (32). Date of Electronic Publication: 2024 Aug 07.
DOI:	10.1523/JNEUROSCI.1970-23.2024
Abstrakt:	Overexpression of the agouti-signaling 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 behavior (ALB). Standard behavioral 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 characterized by pronounced freezing behavior and increased linear and angular swimming velocities. asip1 -Tg animals exhibited low central serotonin (5-HT) 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. Competing Interests: The authors declare no competing financial interests. (Copyright © 2024 the authors.)
Databáze:	MEDLINE
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