5. Conclusion
The presented screening technique provides researchers with a valuable
investigative tool for studying the biological pathways in sensory-motor
systems. This can be particularly useful in future work regarding
systems that may be involved in zebrafish response to electricity along
with examining larvae’s locomotor response, on-demand genetic testing
and in both toxicology and drug screening applications. Employing a
microscope with a larger FOV, along with further modifications to the
device, could increase the number of fish tested at the same time to
improve the throughput of behavioral assays with the presented
technology.
The functional assay presented in this research enabled us to
distinguish the actions of receptor antagonists from those of agonists.
We assessed alteration in electric-induced locomotor activity of
zebrafish larvae following acute exposure to a variety of selective or
non-selective DA antagonists and agonists. Behavioral profiles varied
according to each DA receptor drug in terms of RD and TBF. Exposure to
quinpirole was found to significantly increase the RD and TBF of the
larval response to electric stimulus, suggesting the involvement of
D2-like DA receptors in modulating zebrafish larvae electric induced
response. In contrast, no significant difference resulted due to
exposure to apomorphine and SKF-81297. Treatment to any of the three DA
antagonists decreased RD and TBF, however, only apomorphine and
quinpirole restored the response, reversing the impact of the
antagonists. These results may support the claim that there are similar
actions in mammals and zebrafish triggered by DA receptor drugs.
Additional studies are required to pharmacologically clarify DAergic
receptors’ role and involvement in the zebrafish nervous system.
Although present reports typically match mammalian reports of impacted
movement as a result of induced changes to the DAergic system, further
work is needed to eliminate the possibility of effects on other
signaling pathways. The drugs tested have higher affinities for DAergic
targets. However, they cannot be solely DAergic receptor ligands.
Previous research has shown that these chemicals can also bind to
adrenergic, cholinergic, histaminergic, and serotonergic receptors but
with lower affinity[57–59]. Additional research
is needed to determine the relative affinities for these receptors to
fill this knowledge gap. Internal concentrations would also need to be
determined to eliminate all ambiguity regarding the amount of a drug
successfully passing biological membranes such as the skin or the
blood-brain barrier to be able to interact with the receptors in the
brain. The proposed studies will advance the understanding of
electric-induced behaviors in a lower vertebrate model recognized for
high-throughput and high-content analysis.