Repeated morphine exposure activates synaptogenesis and other neuroplasticity-related gene networks in the prefrontal cortex of male and female rats

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Repeated morphine exposure activates synaptogenesis and other neuroplasticity-related gene networks in the prefrontal cortex of male and female rats

View ORCID ProfileShirelle X. Liu, Mari S. Gades, Andrew H. Harris, Phu V. Tran, Jonathan C. Gewirtz

doi: https://doi.org/10.1101/2020.02.26.966416

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Abstract

Background Opioid abuse is a chronic disorder likely involving stable neuroplastic modifications. While a number of molecules contributing to these changes have been identified, the broader spectrum of genes and gene networks that are affected by repeated opioid administration remain understudied.

Methods We employed Next-Generation RNA-sequencing (RNA-seq) to investigate changes in gene expression in adult male and female rats’ prefrontal cortex (PFC) following daily injection of morphine (5.0 mg/kg) for 10 days. Ingenuity Pathway Analysis (IPA) was used to analyze affected molecular pathways, gene networks, and associated regulatory factors.

Results 90% of differentially expressed genes (DEGs) were upregulated in both males and females, with a 35% overlap between sexes. A substantial number of DEGs play roles in synaptic signaling and neuroplasticity. Although broadly similar, some differences were revealed in the gene ontology networks enriched in females and males (e.g., the endocannabinoid pathway in females and neuroinflammation in males).

Conclusions Our results cohere with findings from previous studies based on a priori gene selection, while identifying broader gene networks activated by repeated opioid exposure. Our results also reveal novel genes and molecular pathways that are upregulated by repeated morphine exposure.

Footnotes

• Role of Funding Source: This work was supported by grants from the Engdahl Family Research Fund and the Office of the Vice President for Research, University of Minnesota, and by T32 DA007097.

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