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This study utilized a novel design to investigate the sensitivity of D2 dopamine receptors to modulating compounds through multiple exposures over early development of zebrafish larvae. Zebrafish were dosed for 30 minutes from 5-8 days post fertilization (dpf) with 16µ/mol of either a D2 antagonist, haloperidol, or a D2 agonist, quinpirole hydrochloride. Two other groups were then dosed with these compounds from 9-12dpf. The effects of D2 receptor modulation were measured by analyzing motor activity on measures of movement distance, frequency, and velocity. Results indicated that larvae dosed with haloperidol on 5dpf had increased activity after the first dosage, but these differences lessened over days 6-8dpf. While conversely, the quinpirole group displayed a decrease in movement activity during trials but in this case, there was a greater deviation from control on trials during 7 and 8dpf. These effects were not observed in subjects dosed from 9-12dpf, which displayed no significant differences from control activity, supporting the hypothesis that those dosed earlier in development would experience greater impacts of D2 modulation. Follow up testing at 16-18dpf did not result in statistically significant differences across treatments, but there were trends on all three measures of lower activity in the quinpirole 5-8dpf group and increased levels of activity in the haloperidol 5-8dpf group. Taken together, these results provide further support for use of Danio rerio larval locomotor activity as a measure of D2 receptor modulation as well as evidence for differential impacts on dopaminergic activity dependent upon the period of drug administration.
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McRoberts, Isaiah Thomas, "The Effects of D2 Receptor Modulation on Locomotor Development in Danio rerio" (2022). Senior Projects Spring 2022. 253.
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