Investigating Psychopharmaceutical Effects on Early Vertebrate Development Using a Zebrafish Model System

TL;DR

This study uses zebrafish to show that certain psychopharmaceuticals disrupt cholesterol and development, leading to abnormal behavior.

Contribution

A high-throughput zebrafish model was developed to assess psychopharmaceutical effects on cholesterol and early vertebrate development.

Findings

Exposure to psychopharmaceuticals increased 7-dehydrocholesterol levels in zebrafish.

Psychopharmaceuticals altered gene expression, brain structure, and behavior in zebrafish.

The zebrafish model effectively detected developmental disruptions caused by cholesterol-altering drugs.

Abstract

Cholesterol homeostasis is necessary for normal vertebrate development. The disruption of cholesterol homeostasis can cause abnormal body and nervous system development and lead to dysfunctional behavior and increased mortality. Commonly prescribed psychopharmaceuticals can alter cholesterol synthesis and may disrupt early vertebrate development. A high-throughput vertebrate zebrafish model system was used to test the hypothesis that exposure to psychopharmaceutical medications alters cholesterol biosynthesis and disrupts gene transcription, early whole-body and brain development, and nervous system function, resulting in abnormal behavior. Exposure to cariprazine, aripiprazole, trazodone, and AY9944 increased 7-dehydrocholesterol levels compared to vehicle-treated zebrafish. Significant differences in disease-associated gene expression, brain structure, and functional behaviors were observed in psychopharmaceutical and AY9944-treated zebrafish compared to controls. These data reveal that the high-throughput zebrafish model system can discern psychopharmaceutical effects on cholesterol synthesis, gene transcription, and key features of early vertebrate development that influences behavior.

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