Abstract
Methamphetamine (MA) use disorder is a chronic neuropsychiatric disease characterized by recurrent binge episodes, intervals of abstinence, and relapses to MA use. Therefore, identification of the key genes and pathways involved is important for improving the diagnosis and treatment of this disorder. In this study, high-throughput RNA sequencing was performed to find the key genes and examine the comparability of gene expression between whisker follicles and the striatum of rats following MA self-administration. A total of 253 and 87 differentially expressed genes (DEGs) were identified in whisker follicles and the striatum, respectively. Multivariate and network analyses were performed on these DEGs to find hub genes and key pathways within the constructed network. A total of 129 and 49 genes were finally selected from the DEG sets of whisker follicles and of the striatum. Statistically significant DEGs were found to belong to the classes of genes involved in nicotine addiction, cocaine addiction, and amphetamine addiction in the striatum as well as in Parkinson’s, Huntington’s, and Alzheimer’s diseases in whisker follicles. Of note, several genes and pathways including retrograde endocannabinoid signaling and the synaptic vesicle cycle pathway were common between the two tissues. Therefore, this study provides the first data on gene expression levels in whisker follicles and in the striatum in relation to MA reward and thereby may accelerate the research on the whisker follicle as an alternative source of biomarkers for the diagnosis of MA use disorder.
Highlights
Methamphetamine (MA) is a highly addictive psychostimulant whose abuse frequently leads to physical and psychological dependence
Repeated consumption of drugs such as cocaine and MA can cause the transition from casual to compulsive drug use, and this transition is thought to be initiated by neuroadaptive changes in brain circuits involved in drug rewards and cognitive processes that regulate habitual behaviors [4,5]
These neuroadaptive changes are commonly caused by complicated alterations of gene expression implicated in transcriptional regulation, synaptic plasticity, and intracellular signaling pathways in brain regions related to drug addiction [6,7]
Summary
Methamphetamine (MA) is a highly addictive psychostimulant whose abuse frequently leads to physical and psychological dependence. Repeated consumption of drugs such as cocaine and MA can cause the transition from casual to compulsive drug use, and this transition is thought to be initiated by neuroadaptive changes in brain circuits involved in drug rewards and cognitive processes that regulate habitual behaviors [4,5]. These neuroadaptive changes are commonly caused by complicated alterations of gene expression implicated in transcriptional regulation, synaptic plasticity, and intracellular signaling pathways in brain regions related to drug addiction [6,7]. It may be worthwhile to investigate the change of gene expression patterns in the striatum during MA self-administration for speeding up the diagnosis and treatment of MA use disorder
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