Abstract
Transcriptome profiling can broadly characterize drug effects and risk for addiction in the absence of drug exposure. Modern large-scale molecular methods, including RNA-sequencing (RNA-Seq), have been extensively applied to alcohol-related disease traits, but rarely to risk for methamphetamine (MA) addiction. We used RNA-Seq data from selectively bred mice with high or low risk for voluntary MA intake to construct coexpression and cosplicing networks for differential risk. Three brain reward circuitry regions were explored, the nucleus accumbens (NAc), prefrontal cortex (PFC), and ventral midbrain (VMB). With respect to differential gene expression and wiring, the VMB was more strongly affected than either the PFC or NAc. Coexpression network connectivity was higher in the low MA drinking line than in the high MA drinking line in the VMB, oppositely affected in the NAc, and little impacted in the PFC. Gene modules protected from the effects of selection may help to eliminate certain mechanisms from significant involvement in risk for MA intake. One such module was enriched in genes with dopamine-associated annotations. Overall, the data suggest that mitochondrial function and glutamate-mediated synaptic plasticity have key roles in the outcomes of selective breeding for high versus low levels of MA intake.
Highlights
There is expansive literature on genome-wide transcriptome profiling results for excessive alcohol consumption and related behaviors [1,2,3,4]
MA high drinking (MAHDR) mice consumed significantly more MA than methamphetamine low drinking (MALDR) mice at every generation, and MA intake declined across generations in the MALDR line (p < 0.001)
The effects are broad and it would be difficult to argue for the importance of a single target
Summary
There is expansive literature on genome-wide transcriptome profiling results for excessive alcohol consumption and related behaviors [1,2,3,4]. Martin et al [5] examined the effects of an acute 20 mg/kg dose of MA on rat nucleus accumbens (NAc) gene expression and identified changes in the expression of genes involved in cell-to-cell signaling, behavioral performance, and the regulation of gene expression. Global miRNA expression array profiling in the NAc of rats treated with escalating doses of MA over a. 15-day period, implicated miRNAs with roles in mitogen-activated protein kinase, cAMP response element binding protein, G-protein coupled receptor, and gonadotropin-releasing hormone signaling pathways [7]. In rats pretreated with MA that subsequently expressed greater conditioned reward and
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.