Fig. 1

(a-f): Behavioral effects of methylphenidate (MPH) and atomoxetine (ATX) treatment for 8 days in zebrafish. Novel tank test was performed in 10 fish per group for 10-min period. a: Schematic representation of novel tank test. b-d: Representative traces of zebrafish in Control (CTL) (b), MPH-treated (c), and ATX-treated fish (d). e: Time spent in top area (s). f: Time spent in bottom area (s). Student’s t-test was performed for statistical analysis and asterisk denotes p < 0.05. (g-j): Differentially expressed genes (DEGs) in the brains of zebrafish treated with MPH or ATX. g: Venn diagram shows the total number of DEGs among controls, MPH-treated and ATX-treated fish. Analysis of differential expression in each cohort resulted in 223 DEGs between MPH-treated and controls, and 68 DEGs between MPH-treated and controls. Comparison of the MPH- and ATX-treated fish to the controls resulted in 18 shared genes with significant differential expression. The DEGs were defined as genes with false discovery rate of less than 0.25 and absolute value of fold change larger than 1.2. h: KEGG pathway analysis for each DEG. Significantly enriched pathways are shown for DEGs in each group (adjusted p-value< 0.05). DEGs in MPH-treated fish are shown in pink, ATX-treated fish in blue, and shared DEGs between MPH- and ATX-treated fish in green. i: Heatmap shows shared DEGs between MPH- and ATX-treated fish (rows) and drug exposure (columns). Genes that have human orthologs are highlighted in green. Blue represents down-regulated expression, red represents up-regulated expression, and white represents no change in expression. j: Network analysis for shared DEGs which have human orthologs. The zebrafish gene names were converted to the human names. Green nodes represent the query and grey nodes represent the results. Network was drawn based on co-expression (purple edges), predicted networks (orange edges), and co-localization (blue edges)