Domperidone up ‐regulates dopamine receptor expression and stimulates locomotor activity in larval zebrafish (Danio rerio)

The objectives of this study were to (1) quantify the temporal expression of transcripts (dopamine receptors, transporters, and tyrosine hydroxylase) associated with dopamine signaling during early stages of zebrafish development and to (2) determine their expression profiles following treatment with a D2 receptor antagonist domperidone (DMP). We also assessed locomotor behavior following treatment with domperidone using alternating periods of light and dark (i.e. dark photokinesis), as dopamine plays a key role in behavior. Relative expression levels of transcripts that were investigated and related to the dopamine system were detected after the first 24 hours post‐fertilization (hpf). Some dopamine receptor transcripts (e.g. drd4c) increased in abundance earlier in the embryo compared to other receptors (e.g. drd3), suggesting that dopamine receptor paralogs may have unique roles in development. Treatment of larvae with DMP resulted in the upregulation of dopamine receptor transcripts (i.e., drd1, drd7, drd4b, drd4c) and dopamine transporter 1 (i.e., slc6a3), and it is hypothesized that up‐regulation of genes related to the dopamine system is a compensatory neurophysiological response to dopamine receptor antagonism. Larval activity during dark photokinesis (measured by distance traveled) was also elevated by DMP. We hypothesize that behavioral responses observed with DMP may be related to the regulation of deep brain photoreception in ZF larvae by dopamine.
Source: Genes, Brain and Behavior - Category: Genetics & Stem Cells Authors: Tags: ORIGINAL ARTICLE Source Type: research