From Mammals to Zebrafish, via Cichlids: Advantages and Some Limits of Fish Models for Human Behavioral Pathologies

Zebrafish (ZF) have gained increasing attention in developmental neuroscience due to their experimental tractability, favorable ethical profile, and translational value. However, the expanding use of the ZF model has also highlighted the need to consider species-specific differences in relation to early social and emotional development. This review adopts a comparative and ethological perspective to examine early social interactions in ZF and mammals, integrating evidence from non-altricial vertebrates and teleost species with parental care (cichlids). Selected illustrative ZF papers were discussed, while Cichlids fish were chosen as a complementary, translationally consistent subject for developmental behavioral studies. The analysis focuses on developmental stages that are relevant for behavioral phenotyping in models of neuropsychiatric conditions. Zebrafish offer multiple methodological advantages, including suitability for high-throughput experimentation and substantial genetic and neurobiological homologies with humans. Nevertheless, the absence of mother–offspring bonding limits the modeling of neurodevelopmental processes shaped by early caregiving, such as imprinting and reciprocal regulatory interactions, instead observed in cichlids. Accumulating evidence indicates that early interactions among age-matched ZF are measurable, developmentally regulated, and sensitive to environmental and experimental manipulations. Within a comparative approach, these early conspecific interactions could be analogs of early social bonding observed in altricial mammals. Rather than representing a critical limitation, such species-specific features can inform the investigation of fundamental mechanisms of social development and support the complementary use of ZF and mammalian models. A contextualized and integrative approach may therefore enhance the translational relevance of ZF-based research, particularly for the study of neurodevelopmental disorders involving early social dysfunction.

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Journal
International Journal of Translational Medicine
Published
2026-01-30
DOI
https://doi.org/10.3390/ijtm6010008
Primary Topic
Zebrafish Biomedical Research Applications
Type
article
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article

From Mammals to Zebrafish, via Cichlids: Advantages and Some Limits of Fish Models for Human Behavioral Pathologies

Daniela Santucci, Arianna Racca, Francesco Ciabattoni, ENRICO ALLEVA
International Journal of Translational Medicine
Zebrafish Biomedical Research Applications
article

From Mammals to Zebrafish, via Cichlids: Advantages and Some Limits of Fish Models for Human Behavioral Pathologies

Daniela Santucci, Arianna Racca, Francesco Ciabattoni, ENRICO ALLEVA
article en

Abstract

Zebrafish (ZF) have gained increasing attention in developmental neuroscience due to their experimental tractability, favorable ethical profile, and translational value. However, the expanding use of the ZF model has also highlighted the need to consider species-specific differences in relation to early social and emotional development. This review adopts a comparative and ethological perspective to examine early social interactions in ZF and mammals, integrating evidence from non-altricial vertebrates and teleost species with parental care (cichlids). Selected illustrative ZF papers were discussed, while Cichlids fish were chosen as a complementary, translationally consistent subject for developmental behavioral studies. The analysis focuses on developmental stages that are relevant for behavioral phenotyping in models of neuropsychiatric conditions. Zebrafish offer multiple methodological advantages, including suitability for high-throughput experimentation and substantial genetic and neurobiological homologies with humans. Nevertheless, the absence of mother–offspring bonding limits the modeling of neurodevelopmental processes shaped by early caregiving, such as imprinting and reciprocal regulatory interactions, instead observed in cichlids. Accumulating evidence indicates that early interactions among age-matched ZF are measurable, developmentally regulated, and sensitive to environmental and experimental manipulations. Within a comparative approach, these early conspecific interactions could be analogs of early social bonding observed in altricial mammals. Rather than representing a critical limitation, such species-specific features can inform the investigation of fundamental mechanisms of social development and support the complementary use of ZF and mammalian models. A contextualized and integrative approach may therefore enhance the translational relevance of ZF-based research, particularly for the study of neurodevelopmental disorders involving early social dysfunction.

International Journal of Translational MedicineVol. 6(1)
Istituto Superiore di Sanità (IT), Sapienza University of Rome (IT)
Openalex Percentile: Top 73%
Zebrafish Biomedical Research Applications
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