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Manipulating IncRNAs to Disrupt Reconsolidation of Methamphetamine Associated Memories

操纵 IncRNA 破坏甲基苯丙胺相关记忆的重新巩固

基本信息

批准号：
9182423
负责人：
Courtney A Miller
金额：
$ 28.8万
依托单位：
SCRIPPS FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-07-01 至 2018-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9182423
关键词：
Abstinence Adult Amygdaloid structure Animal Model Award Behavior Bioinformatics Brain Brain region Cell Nucleus Cues Cytoplasm Data Drug usage Emotional Epigenetic Process Extinction (Psychology)Gene Expression Genetic Translation Genome Goals Gold Hippocampus (Brain)Image Large-Scale Sequencing Medial Mediating Memory Messenger RNA Methamphetamine Methamphetamine dependence Modeling Modification Molecular Profiling Mus Nervous system structure Neurons Nucleotides Outcome Pharmaceutical Preparations Population Prefrontal Cortex Process Protein Biosynthesis Rattus Rehabilitation therapy Relapse Role Selection Criteria Self Administration Sequence Analysis Specificity Staging Substance Use Disorder Synaptic plasticity Testing Therapeutic Untranslated RNA Ursidae Family Work clinically relevant craving design drug reward genome-wide in vivo innovation insight mRNA Stability new therapeutic target next generation sequencing novel preference prevent psychostimulant research study transcriptome transcriptome sequencing treatment strategy

项目摘要

PROJECT SUMMARY Currently, clinicians can offer little hope to people addicted to psychostimulants, such as methamphetamine (METH). The memories associated with drug use and reward can bear a powerful motivational influence over behavior. Accordingly, the field is now working to develop strategies to manipulate the extinction and reconsolidation of cue-drug associations as novel treatment strategies to reduce their power to induce craving and relapse. Here we propose to study the contribution of a novel class of candidates, long- noncoding RNAs (lncRNAs), to METH-associated memory. An increasing number of functional studies indicate lncRNAs participate as regulators at almost every stage of gene expression, from epigenetic modifications in the nucleus to mRNA stability and translation in the cytoplasm. This regulatory potential, along with the abundance of lncRNAs, implies that lncRNAs may be part of a broad epigenetic network. Despite these functional insights, only a small number of lncRNAs have been studied in the nervous system and their contribution to substance use disorder (SUD) is unknown. Because of the transcriptional and translational roles lncRNAs, elucidating their function in regions of brain implicated in SUD will help identify novel therapeutic targets. The central hypothesis of this proposal, derived from our own preliminary studies, is that specific lncRNAs mediate reconsolidation of METH-associated memories. To test this hypothesis, we will employ animal models of drug seeking and relapse to identify and manipulate specific lncRNAs in vivo with the goal of preventing relapse by blocking reconsolidation.

项目总结