Dopamine disruption and autism phenotypes in slc6a3-/- zebrafish: Behavioural and molecular insights

Dopamine plays a crucial role in regulating movement, motivation, attention, and emotions. Disruptions in dopamine metabolism have been linked to various psychiatric disorders, including autism spectrum disorder (ASD). In this study, we generated an slc6a3 knockout zebrafish model using the CRISPR-Cas9 system to investigate the relationship between dopamine dysfunction and autism. Our results revealed that slc6a3 knockout significantly reduced dopamine levels, leading to impaired dopamine synthesis, transport, and metabolism. Behavioural analysis demonstrated that slc6a3-/- zebrafish exhibited decreased motor activity, increased anxiety-like behaviour, and autism-related symptoms, such as impaired social ability and "digging" behaviour. Pharmacological intervention with risperidone and clozapine improved motor function, social interaction, and anxiety levels, with risperidone showing superior effects. Transcriptomic analysis identified significant changes in several nervous system-related genes in slc6a3-/- zebrafish, suggesting that these gene alterations may contribute to the observed behavioural abnormalities. Our study highlights the crucial role of dopamine dysfunction in autism and establishes slc6a3-/- zebrafish as a valuable model for studying autism and screening potential therapeutic drugs.