Differential effects of acute administration of SCH-23390, a D1 receptor antagonist, and of ethanol on swimming activity, anxiety-related responses, and neurochemistry of zebrafish

The zebrafish has become an increasingly popular animal model for investigating ethanol's actions in the brain and its effects on behavior. Acute exposure to ethanol in zebrafish has been shown to induce a dose-dependent increase of locomotor activity, to reduce fear- and anxiety-related behavioral responses, and to increase the levels of dopamine and its metabolite 3,4-dihydroxyphenylacetic acid (DOPAC). The objective of the present study was to investigate the role of dopamine D-1 receptors (D-1-R) in ethanol-induced locomotor activity in zebrafish. Zebrafish were pre-treated with SCH-23390 (0 or 1 mg/L bath concentration), a D-1-R antagonist, and subsequently exposed to ethanol (0, 0.25, 0.5, 1.0 % v/v). To explore potential underlying mechanisms, we quantified levels of dopamine, DOPAC, serotonin, and 5-HIAA from whole-brain tissue using high-precision liquid chromatography. We found pre-treatment with the D-1-R antagonist to attenuate locomotor activity independent of ethanol concentration. Furthermore, unlike ethanol, D-1-R antagonism did not alter behavioral responses associated with fear and anxiety. Pre-treatment with SCH-23390 decreased levels of dopamine and DOPAC, but this effect was also independent of ethanol concentration. The D-1-R antagonist also reduced serotonin and 5-hydroxyindole acetic acid (5-HIAA) levels. These results suggest a multifaceted and at least partially independent role of dopamine D-1 receptors in ethanol-induced locomotor activity and anxiety-related responses as well as in the functioning of the dopaminergic and serotoninergic neurotransmitter systems in zebrafish.