Chronic Oxycodone Self-administration Altered Reward-related Genes in the Ventral and Dorsal Striatum of C57BL/6J Mice: An RNA-seq Analysis

• Published in: Neuroscience Vol. 393; pp. 333 - 349
• Main Authors: Zhang, Yong, Liang, Yupu, Randesi, Matthew, Yuferov, Vadim, Zhao, Connie, Kreek, Mary Jeanne
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 21.11.2018
• Subjects: Analgesics, Opioid - administration & dosage; Analgesics, Opioid - pharmacology; Animals; Behavior, Addictive - drug therapy; C57BL/6J mice; Gene Expression - drug effects; Male; Mice, Inbred C57BL; Opioid-Related Disorders - metabolism; Oxycodone - administration & dosage; Oxycodone - pharmacology; oxycodone self-administration; Reward; reward-related genes; RNA sequencing; Self Administration - methods; Sequence Analysis, RNA - methods; Ventral Striatum - drug effects; Ventral Striatum - metabolism; RNA sequencing; oxycodone self-administration; Glra1; Galr1; SA; Ct; reward-related genes; C57BL/6J mice; Pomc; Htr7; RNA-seq; SNP; Htr2a; qPCR
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2018.07.032

•Oxycodone SA altered 32 reward-related genes in the ventral striatum assessed by RNA-seq.•Oxycodone SA altered 7 reward-related genes in the dorsal striatum assessed by RNA-seq.•The amount of oxycodone SA is correlated with gene expression levels of some genes. Prescription opioid abuse, for example of oxycodone, is a pressing public health issue. This study focuses on how chronic oxycodone self-administration (SA) affects the reward pathways in the mouse brain. In this study, we tested the hypothesis that the expression of reward-related genes in the ventral and dorsal striatum, areas involved in different aspects of opioid addiction models, was altered within 1 h after chronic oxycodone SA, using transcriptome-wide sequencing (RNA-seq). Based on results from earlier human genetic and rodent preclinical studies, we focused on a set of genes that may be associated with the development of addictive diseases and the rewarding effect of drugs of abuse, primarily in the opioid, stress response and classical neurotransmitter systems. We found that 32 transcripts in the ventral striatum, and 7 in the dorsal striatum, were altered significantly in adult mice that had self-administered oxycodone (n = 5) for 14 consecutive days (4 h/day) compared with yoked saline controls (n = 5). The following 5 genes in the ventral striatum showed experiment-wise significant changes: proopiomelanocortin (Pomc) and serotonin 5-HT-2A receptor (Htr2a) were upregulated; serotonin receptor 7 (Htr7), galanin receptor1 (Galr1) and glycine receptor 1 (Glra1) were downregulated. Some genes detected by RNA-seq were confirmed by quantitative polymerase chain reaction (qPCR). Conclusion: A RNA-seq study shows that chronic oxycodone SA alters the expression of several reward-related genes in the dorsal and ventral striatum. These results suggest potential mechanisms underlying neuronal adaptation to chronic oxycodone self-exposure, of relevance to our mechanistic understanding of prescription opioid abuse.