Regional analysis of the brain transcriptome in mice bred for high and low methamphetamine consumption

Robert Hitzemann, Ovidiu Iancu, Cheryl Reed, Harue Baba, Denesa R. Lockwood, Tamara Phillips

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number155
JournalBrain Sciences
Volume9
Issue number7
DOIs
StatePublished - Jul 1 2019

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Methamphetamine
Gene Expression Profiling
Nucleus Accumbens
Brain
Mesencephalon
Prefrontal Cortex
Drinking
RNA
RNA Sequence Analysis
Neuronal Plasticity
Gene Regulatory Networks
Reward
Pharmaceutical Preparations
Glutamic Acid
Dopamine
Alcohols
Gene Expression
Genes

Keywords

  • Addiction
  • Coexpression network
  • Connectivity
  • Cosplicing network
  • Gene expression
  • Nucleus accumbens
  • Prefrontal cortex
  • RNA-Seq
  • Selective breeding
  • Ventral midbrain

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Regional analysis of the brain transcriptome in mice bred for high and low methamphetamine consumption. / Hitzemann, Robert; Iancu, Ovidiu; Reed, Cheryl; Baba, Harue; Lockwood, Denesa R.; Phillips, Tamara.

In: Brain Sciences, Vol. 9, No. 7, 155, 01.07.2019.

Research output: Contribution to journalArticle

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