mRNA and microRNA analysis reveals modulation of biochemical pathways related to addiction in the ventral tegmental area of methamphetamine self-administering rats

BMC Neuroscience

B M Kivell³  D Macartney-Coxson²  M C Benton¹  P J Bosch³ 

[1] Genomics Research Centre, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia;Institute of Environmental Science and Research, Wellington, New Zealand;Centre for Biodiscovery, School of Biological Sciences, Victoria University of Wellington, Kelburn Parade, Wellington 6140, New Zealand

关键词: microRNA;    Self-administration;    Methamphetamine;    Genetics;    Brain;   

Others  :  1220307
DOI  :  10.1186/s12868-015-0186-y

 received in 2015-02-09, accepted in 2015-07-14,  发布年份 2015

【 摘 要 】

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.

Conclusion

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.

【 授权许可】

   
2015 Bosch et al.

【 图 表 】

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