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Published on: September 16, 2015
Mechanisms underlying microRNA-222-3p modulation of methamphetamine-induced conditioned place preference in the
Qing Shang1,2, Jing Wang1,2, Zhijia Xi1,2
1Institute of Forensic Injury, Institute of Forensic Bio-Evidence, Western China Science and Technology Innovation Harbor, Xi'an Jiaotong University, Xi'an, People's Republic of China.
Rationale:
MicroRNA (miRNA) control of post-transcription gene expression in the nucleus accumbens (NAc) has been implicated in methamphetamine (METH) dependence. Conditioned place preference (CPP) is a classical animal procedure that reflects the rewarding effects of addictive drugs. miR-222-3p has been reported to play a key role in various neurological diseases and is strongly associated with alcohol dependence. Nevertheless, the role of miR-222-3p in METH dependence remains unclear.
Objective:
To explore the molecular mechanisms underlying the role of miR-222-3p in the NAc in METH-induced CPP.
Methods:
miR-222-3p expression in the NAc of METH-induced CPP mice was detected by quantitative real-time (qPCR). Following adeno-associated virus (AAV)-mediated overexpression or knockdown of miR-222-3p in the NAc, mice were subjected to CPP to investigate the effects of miR-222-3p on METH-induced CPP. Target genes of mir-222-3p were predicted using bioinformatics analysis. Candidate target genes for METH-induced CPP were validated by qPCR.
Results:
miR-222-3p expression in the NAc was decreased in CPP mice. Overexpression of miR-222-3p in the NAc blunted METH-induced CPP. Ppp3r1, Cdkn1c, Fmr1, and PPARGC1A were identified as target gene transcripts potentially mediating the effects of miR-222-3p on METH-induced CPP.
Conclusion:
Our results highlight miR-222-3p as a key epigenetic regulator in METH-induced CPP and suggest a potential role for miR-222-3p in the regulation of METH-induced reward-related changes in the brain.
Insights
MicroRNA-222-3p, a key epigenetic regulator, is decreased in the nucleus accumbens during methamphetamine dependence. Restoring its levels reduces drug-induced reward behaviors, suggesting a therapeutic target.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- MicroRNA (miRNA) regulation of gene expression in the nucleus accumbens (NAc) is crucial for understanding methamphetamine (METH) dependence.
- While miR-222-3p is linked to other neurological conditions and alcohol dependence, its specific role in METH dependence is not well understood.
Purpose of the Study:
- To investigate the function of miR-222-3p within the NAc in the context of METH-induced conditioned place preference (CPP).
- To elucidate the molecular mechanisms by which miR-222-3p influences METH reward pathways.
Main Methods:
- Quantitative real-time PCR (qPCR) was used to measure miR-222-3p expression in the NAc of METH-CPP mice.
- Adeno-associated virus (AAV) vectors were employed for in vivo overexpression and knockdown of miR-222-3p in the NAc.
- Bioinformatics analysis predicted target genes, which were subsequently validated using qPCR.
Main Results:
- miR-222-3p expression was significantly reduced in the NAc of mice exhibiting METH-induced CPP.
- Overexpression of miR-222-3p in the NAc attenuated the development of METH-induced CPP.
- Potential target genes, including Ppp3r1, Cdkn1c, Fmr1, and PPARGC1A, were identified as mediators of miR-222-3p's effects.
Conclusions:
- miR-222-3p acts as a critical epigenetic regulator in the neurobiological processes underlying METH-induced CPP.
- These findings suggest that miR-222-3p plays a significant role in modulating METH-induced reward-related brain changes.
- miR-222-3p represents a potential therapeutic target for mitigating METH dependence.
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