Abstract
BackgroundMicroRNA (miRNA) emerges as important player in drug abuse. Yet, their expression profile in neurological disorder of cocaine abuse has not been well characterized. Here, we explored the changes of miRNA expression in rat hippocampus following repeated cocaine exposure and subsequent abstinence from cocaine treatment.ResultsConditioned place preference (CPP) procedure was used to assess the acquisition and extinction of cocaine-seeking behavior in rats. MiRNA microarray was performed to examine miRNAs levels in rat hippocampus. Quantitative RT-PCR was conducted to further confirm results in microarray study. Finally, bioinformatic predictions were made to suggest potential target genes of cocaine-responsive miRNA in this study. MiRNA array found that 34 miRNA levels were changed in rat hippocampus while acquiring cocaine CPP and 42 miRNAs levels were altered after the cocaine-induced CPP were extinguished, as compared to normal controls. The findings from qRT-PCR study support results from microarray analysis.ConclusionsThe current study demonstrated dynamic changes in miRNA expression in rat hippocampus during the acquisition and extinction of cocaine-induced CPP. Some miRNAs which have been previously reported to be involved in brain disorders and drug abuse, including miR-133b, miR-134, miR-181c, miR-191, miR-22, miR-26b, miR-382, miR-409-3p and miR-504, were found to be changed in their expression following repeated cocaine exposure and subsequent abstinence from cocaine treatment. These findings may extend our understanding of the regulatory network underlying cocaine abuse and may provide new targets for the future treatment of drug abuse.
Highlights
MicroRNA emerges as important player in drug abuse
Microarray study showed that 33 miRNAs levels were upregulated and 9 miRNAs levels were down-regulated in hippocampus in CCE rats on day 26, as compared to that in SCE rats
Our result indicates that miRNA expression profiles of hippocampus are different in cocaine conditioned place preference (CPP)-acquiring phase and CPP-extinguishing phase
Summary
MicroRNA (miRNA) emerges as important player in drug abuse. Yet, their expression profile in neurological disorder of cocaine abuse has not been well characterized. Lots of genes have been identified to play important roles in the development of cocaine addiction [4,5]. Many of these genes exert their regulatory functions on cocaine abuse by forming a complex regulatory network. Deficiency of argonaute 2 (Ago2), a regulator site for miRNA-mediated gene silencing, in dopamine receptor 2-expressed neurons significantly reduces the motivation of cocaine intake in mice [11]. All these studies indicate that miRNAs may play important roles in the development of cocaine abuse. MiRNAs may be considered as “master regulators” or “bridge regulators” of gene expression
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