Dopamine D₁ and D₂ receptor antagonism during development alters later behavior in zebrafish

This study sought to examine the long-term behavioral impacts of dopamine D₁ and D₂ receptor antagonism during development in zebrafish (Danio rerio). Zebrafish embryos of both the AB* and 5D strains were exposed via immersion to either the D₁ receptor antagonist SCH-23,390 or the D₂ receptor antagonist haloperidol, at either 0.5 or 1.5-μM, from 5 h post-fertilization to 5 days post-fertilization. Aquarium water served as a control. Fish were then either tested as larvae on day 6 post-fertilization on a light/dark locomotor assay, or were grown to adulthood and tested on a behavioral battery that included assays for novel environment exploration, startle habituation, social affiliation, and predator escape (AB* strain only). Overall, developmental exposure to dopamine D₁ and D₂ receptor antagonists caused clear effects in larval locomotor behavior, driving hyperactivity in dark phases and hypoactivity in light phases. Additionally, control fish from the two strains were significantly different from each other (p < 0.05) with the AB* fish being more active than SD during the dark periods of the test. In the adult behavioral battery, developmental exposure to 1.5-μM of the D₁ antagonist SCH-23390 significantly reduced activity (p < 0.05) in the predator escape assay. Despite the fact that embryonic exposure to D₁ and D₂ receptor antagonists caused clear behavioral alterations in larval activity there were much more subtle effects persisting into adulthood.