Domperidone upregulates dopamine receptor expression and stimulates locomotor activity in larval zebrafish (Danio rerio)

Abstract

Dopamine (DA) plays a significant role in cognition, motor function and social behavior. The objectives of this study were to (1) quantify the temporal expression of transcripts (DA receptors, transporters and tyrosine hydroxylase) associated with DA signaling during early stages of zebrafish development and (2) determine their expression profiles following treatment with a D₂ receptor antagonist domperidone (DMP). We also assessed locomotor behavior following treatment with DMP using alternating periods of light and dark (ie, dark photokinesis), as DA plays a key role in behavior. Relative expression levels of transcripts that were investigated and related to the DA system were detected after the first 24 hours postfertilization (hpf). Some DA receptor transcripts (eg, drd4c) increased in abundance earlier in the embryo compared with other receptors (eg, drd3), suggesting that DA receptor paralogs may have unique roles in development. Treatment of larvae with DMP resulted in the upregulation of DA receptor transcripts (ie, drd1, drd7, drd4b, drd4c) and DA transporter 1 (ie, slc6a3), and it is hypothesized that upregulation of genes related to the DA system is a compensatory neurophysiological response to DA 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 zebrafish (Danio rerio) (ZF) larvae by DA.

Keywords: development; dopamine transporter; neurobehavioral; swimming; tyrosine hydroxylase.