Comparing the Role of Dopamine D1 and D3 Receptors in Mediating Aversive Learning in Zebrafish

Dopamine is a key neuromodulator in the vertebrate brain. Despite accumulating evidence of dopamine's involvement in learning and memory regulation, the roles of individual receptor subtypes remain unclear. This study investigates the effects of SCH-23390 and SB-27011-A, selective antagonists of the D1 and D3 dopamine receptors on learning and memory in zebrafish. Using an associative learning task in a T-maze with electric shocks as stimuli, we assessed the impact of these drugs on zebrafish performance. Our results show that SCH-23390 at both 1 mg/L and 5 mg/L and SB-27011-A at 5 mg/L altered behaviors. However, the effects observed at 5 mg/L were confounded by impaired locomotion, suggesting that reliable cognitive assessments should focus on lower doses. Although no significant differences were observed in percentage of correct arm entries, the SCH-23390 group at 1 mg/L showed a significantly lower proportion of fish with correct first arm entries and significantly more time spent in the wrong arm, whereas no such effects were seen in the SB-27011-A group. These findings suggest that D1 receptors, but not D3 receptors, play a crucial role in associative learning involving aversive stimuli. Further research is necessary to clarify how dopamine receptor subtypes contribute to different learning paradigms.