Cuprizone-induced dopaminergic hyperactivity and locomotor deficit in zebrafish larvae

Cuprizone (CPZ) is a copper-chelator and toxic to mitochondria. Recent studies have shown oligodendrocyte (OL) loss and demyelination along with dopamine (DA) increase and behavioral abnormalities in CPZ-exposed mice, demonstrating its application in schizophrenia research. This study examined effects of CPZ exposure on autonomous behavior and dopaminergic neurotransmission in larval zebra fish. CPZ exposure was found to reduce the swimming velocity of zebra fish thus decreased swimming distance during day and night time. Moreover, the treatment induced a movement response of zebra fish larvae reacting to light-on/off switch featured by swimming velocity increase and decrease during the first and second half of the light-on/off phase, respectively. But, it abolished responses of zebra fish to sound-on/off seen in Control group. HPLC analysis showed elevated DA levels in the zebra fish, no change in NE and 5-HT levels. Transcriptome analysis reported changes in gene expression related to dopaminergic synapse and oxidative phosphorylation in CPZ-exposed larvae relative to Control group. Of the gene expression changes, up-regulation of drd2a, drd2b, drd4a and drd4rs was confirmed by RT-PCR, although no difference existed between Control and CPZ groups in dopaminergic neuron numbers. These results demonstrated dopaminergic hyperactivity and locomotor deficit in CPZexposed zebra fish larvae, encouraging further application of this model in exploring neurotoxic effects of CPZ on mitochondria and dopaminergic neurotransmission in zebra fish.

Automated summary

This study investigated the effects of CPZ exposure on larval zebra fish, showing that CPZ decreased swimming velocity and disrupted responses to light and sound stimulation. Transcriptome analysis revealed changes in genes related to dopaminergic synapse and oxidative phosphorylation. These findings suggest that CPZ induces dopaminergic hyperactivity and locomotor deficits in zebra fish, providing insights for further research on the neurotoxic effects of CPZ on mitochondria and dopaminergic neurotransmission.