Differential effects of dopamine D1 and D2/3 receptor antagonism on motor responses

The zebrafish dopaminergic system is thought to be evolutionarily conserved and may be amenable to pharmacological manipulation using drugs developed for mammalian receptors. However, only few studies have examined the role of specific receptor subtypes in behaviour of adult zebrafish. The objectives of this study are to determine the translational relevance of the zebrafish and examine the psychopharmacology of specific dopamine receptors in this species. Using a behavioural pharmacological approach, we examine the effect of D-1 and D-2/3 receptor antagonisms on motor patterns of adult zebrafish during acute drug exposure and withdrawal. Acute exposure to SCH-23390 (D-1 receptor antagonist) decreased total distance travelled in a dose-dependent manner. Exposure to amisulpride (D-2/3 receptor antagonist) induced a biphasic dose-response in total distance travelled and in angular velocity. The results provide support for the existence of structurally and functionally conserved postsynaptic D-1 and D-2 receptors, as well as presynaptic D-2 autoreceptors in the zebrafish brain. The behavioural effects of the employed antagonists did not persist following 30 min of withdrawal. The results suggest that zebrafish, a cheaper and simpler model organism compared to the rat and the mouse, may be an efficient translationally relevant tool for the analysis of the psychopharmacology of receptors of the vertebrate dopaminergic system.