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Regional Analysis of the Brain Transcriptome in Mice Bred for High and Low Methamphetamine Consumption

1
Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR 97239, USA
2
Methamphetamine Abuse Research Center, Oregon Health & Science University, Portland, OR 97239, USA
3
Veterans Affairs Portland Health Care System, Portland, OR 97239, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Brain Sci. 2019, 9(7), 155; https://doi.org/10.3390/brainsci9070155
Received: 3 June 2019 / Revised: 20 June 2019 / Accepted: 26 June 2019 / Published: 30 June 2019
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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. View Full-Text
Keywords: addiction; coexpression network; connectivity; cosplicing network; gene expression; nucleus accumbens; prefrontal cortex; RNA-Seq; selective breeding; ventral midbrain addiction; coexpression network; connectivity; cosplicing network; gene expression; nucleus accumbens; prefrontal cortex; RNA-Seq; selective breeding; ventral midbrain
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Hitzemann, R.; Iancu, O.D.; Reed, C.; Baba, H.; Lockwood, D.R.; Phillips, T.J. Regional Analysis of the Brain Transcriptome in Mice Bred for High and Low Methamphetamine Consumption. Brain Sci. 2019, 9, 155.

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