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Zebrafish (Danio rerio) are rapidly emerging in biomedicine as promising tools for disease modelling and drug discovery. The use of zebrafish for neuroscience research is also growing rapidly, necessitating novel reliable and unbiased methods of neurophenotypic data collection and analyses. Here, we applied the artificial intelligence (AI) neural network-based algorithms to a large dataset of adult zebrafish locomotor tracks collected previously in a series of in vivo experiments with multiple established psychotropic drugs. We first trained AI to recognize various drugs from a wide range of psychotropic agents tested, and then confirmed prediction accuracy of trained AI by comparing several agents with known similar behavioral and pharmacological profiles. Presenting a framework for innovative neurophenotyping, this proof-of-concept study aims to improve AI-driven movement pattern classification in zebrafish, thereby fostering drug discovery and development utilizing this key model organism., (Copyright © 2021. Published by Elsevier Inc.)

The zebrafish is a promising model species in biomedical research, including neurotoxicology and neuroactive drug screening. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) evokes degeneration of dopaminergic neurons and is commonly used to model Parkinson's disease (PD) in laboratory animals, including zebrafish. However, cognitive phenotypes in MPTP-evoked experimental PD models remain poorly understood. Here, we established an LD50 (292 mg/kg) for intraperitoneal MPTP administration in adult zebrafish, and report impaired spatial working memory (poorer spontaneous alternation in the Y-maze) in a PD model utilizing fish treated with 200 µg of this agent. In addition to conventional behavioral analyses, we also employed artificial intelligence (AI)-based approaches to independently and without bias characterize MPTP effects on zebrafish behavior during the Y-maze test. These analyses yielded a distinct cluster for 200-μg MPTP (vs. other) groups, suggesting that high-dose MPTP produced distinct, computationally detectable patterns of zebrafish swimming. Collectively, these findings support MPTP treatment in adult zebrafish as a late-stage experimental PD model with overt cognitive phenotypes. [ABSTRACT FROM AUTHOR]