Exposure to Morphine and Cocaine Modify the Transcriptomic Landscape in Zebrafish Embryos

• Published in: Neuroscience Vol. 507; pp. 14 - 27
• Main Authors: Calderon-Garcia, Andrés Angel, Perez-Fernandez, Maria, Curto-Aguilera, Daniel, Rodriguez-Martin, Ivan, Sánchez-Barba, Mercedes, Gonzalez-Nunez, Veronica
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 15.12.2022
• Subjects: Animals; Cocaine; Cocaine - pharmacology; DNA methylation; Morphine; Morphine - pharmacology; Receptors, Opioid - metabolism; Transcriptome; Transcriptomic assay; Zebrafish; Zebrafish - metabolism; NAc; APID; Transcriptomic assay; DNA methylation; Morphine; Zebrafish; Cocaine; NGS; HAND; hpf
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2022.10.017

[Display omitted] •Exposure to morphine and cocaine induces changes in the transcriptome of zebrafish embryos.•Pathways related to lipid metabolism appear to be overrepresented for both treatments.•Other deregulated pathways are detoxification, response to chemicals and calcium signalling.•Morphine and cocaine modify global DNA methylation. Morphine and other opioid analgesics are the drugs of election to treat moderate-to-severe pain, and they elicit their actions by binding to the opioid receptors. Cocaine is a potent inhibitor of dopamine, serotonin, and noradrenaline reuptake, as it blocks DAT, the dopamine transporter, causing an increase in the local concentration of these neurotransmitters in the synaptic cleft. The molecular effects of these drugs have been studied in specific brain areas or nuclei, but the systemic effects in the whole organism have not been comprehensively analyzed. This study aims to analyze the transcriptomic changes elicited by morphine (10 uM) and cocaine (15 uM) in zebrafish embryos. An RNAseq assay was performed with tissues extracts from zebrafish embryos treated from 5 hpf (hours post fertilization) to 72 hpf, and the most representative deregulated genes were experimentally validated by qPCR. We have found changes in the expression of genes related to lipid metabolism, chemokine receptor ligands, visual system, hemoglobins, and metabolic detoxification pathways. Besides, morphine and cocaine modified the global DNA methylation pattern in zebrafish embryos, which would explain the changes in gene expression elicited by these two drugs of abuse.