RNA-Seq Analysis of Morphine-Induced Gene Expression Changes in the Mouse Nucleus Accumbens
Seyed Mahmoud Pourmand1, Shahrzad Nazari2, Elham Nazari3
1Department of Addiction, Tehran Institute of Psychiatry, School of Behavioral Sciences and Mental Health, Iran University of Medical Sciences, Tehran, Iran.
Background:
Opioid use disorder (OUD) remains a critical global health challenge. The nucleus accumbens (NAc), a key region of the brain reward system, plays an essential role in opioid-induced neuroadaptations. Characterizing gene expression alterations in reward-system regions, such as the NAc, is essential for elucidating the molecular mechanisms underlying addiction. In recent years, bioinformatics has emerged as a rapidly advancing field and has played a pivotal role in elucidating molecular mechanisms and in advancing computational biology.
Objectives:
This study aimed to characterize transcriptomic changes in the NAc of mice following chronic morphine administration using RNA sequencing and bioinformatic analysis.
Methods:
RNA sequencing (RNA-Seq) data from morphine- and saline-treated mice were obtained from the Gene Expression Omnibus database via the Sequence Read Archive. Following quality control and alignment, differentially expressed genes (DEGs) were identified using the DESeq2 package in R. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, as well as protein-protein interaction (PPI) network analyses, were performed to evaluate the functional implications of these genes.
Results:
Principal component analysis (PCA) revealed distinct transcriptomic profiles between the morphine and control groups. A total of 143 DEGs were identified, including 125 up-regulated and 18 down-regulated genes. Enrichment analyses indicated significant involvement in synaptic signaling, ion transport, and neurodegenerative pathways. Protein-protein interaction (PPI) network analysis identified several hub genes, including fgf3 (fibroblast growth factor 3), mki67 (marker of proliferation Ki-67), grin2a/grin2b (glutamate receptor NMDA subunits 2A/2B), gli1 (GLI family zinc finger 1), and ago2 (argonaute RISC catalytic component 2), which are associated with synaptic plasticity, neurogenesis, and epigenetic regulation.
Conclusions:
Chronic morphine exposure induces widespread gene expression changes in the NAc, engaging pathways associated with synaptic remodeling, neuronal excitability, and addiction-related neuroplasticity. These findings provide a molecular framework for understanding opioid-induced adaptations and identify candidate targets, including N-methyl-D-aspartate (NMDA) receptor subunits, fgf3, and ago2, for potential therapeutic intervention. Future studies should functionally validate these targets and evaluate their translational relevance in the context of OUD.
