title: mRNA and microRNA analysis reveals modulation of biochemical pathways related to addiction in the ventral tegmental area of methamphetamine self-administering rats.
abstract: BACKGROUND
  Methamphetamine is a highly addictive central nervous system stimulant with increasing levels of abuse worldwide. Alterations to mRNA and miRNA expression within the mesolimbic system can affect addiction-like behaviors and thus play a role in the development of drug addiction. While many studies have investigated the effects of high-dose methamphetamine, and identified neurotoxic effects, few have looked at the role that persistent changes in gene regulation play following methamphetamine self-administration. Therefore, the aim of this study was to identify RNA changes in the ventral tegmental area following methamphetamine self-administration. We performed microarray analyses on RNA extracted from the ventral tegmental area of Sprague-Dawley rats following methamphetamine self-administration training (2 h/day) and 14 days of abstinence.
  
  
  RESULTS
  We identified 78 miRNA and 150 mRNA transcripts that were differentially expressed (fdr adjusted p < 0.05, absolute log2 fold change >0.5); these included genes not previously associated with addiction (miR-125a-5p, miR-145 and Foxa1), loci encoding receptors related to drug addiction behaviors and genes with previously recognized roles in addiction such as miR-124, miR-181a, DAT and Ret.
  
  
  CONCLUSIONS
  This study provides insight into the effects of methamphetamine on RNA expression in a key brain region associated with addiction, highlighting the possibility that persistent changes in the expression of genes with both known and previously unknown roles in addiction occur.
authors.affiliation: Centre for Biodiscovery, School of Biological Sciences, Victoria University of Wellington, Kelburn Parade, PO Box 600, Wellington, 6140, New Zealand. peetyrbosch@gmail.com.
authors.forename: P J
authors.initials: PJ
authors.lastname: Bosch
authors.affiliation: Institute of Environmental Science and Research, Wellington, New Zealand. miles.benton84@gmail.com.|Genomics Research Centre, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia. miles.benton84@gmail.com.
authors.forename: M C
authors.initials: MC
authors.lastname: Benton
authors.affiliation: Institute of Environmental Science and Research, Wellington, New Zealand. donia.macartney@esr.cri.nz.
authors.forename: D
authors.initials: D
authors.lastname: Macartney-Coxson
authors.affiliation: Centre for Biodiscovery, School of Biological Sciences, Victoria University of Wellington, Kelburn Parade, PO Box 600, Wellington, 6140, New Zealand. Bronwyn.kivell@vuw.ac.nz.
authors.forename: B M
authors.initials: BM
authors.lastname: Kivell
mesh_terms: D019969:Amphetamine-Related Disorders / Q000378:metabolism; D000818:Animals; D002408:Catheters, Indwelling; D000697:Central Nervous System Stimulants / Q000008:administration & dosage*; D058999:Drug-Seeking Behavior / Q000502:physiology; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage*; D035683:MicroRNAs / Q000378:metabolism*; D046228:Microarray Analysis; D012333:RNA, Messenger / Q000378:metabolism*; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012646:Self Administration; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D000697:Central Nervous System Stimulants; D035683:MicroRNAs; D012333:RNA, Messenger; D008694:Methamphetamine