环状RNAcircTmeff1-Tomoregulin-1调控网络对毒品潜伏心理渴求的影响及其机制研究

持续存在的毒品心理渴求是导致复吸的重要原因。circRNA作为一种重要的调控分子在帕金森、抑郁症等神经系统疾病中发挥重要作用，但在毒品心理渴求中的作用尚未明确。我们前期研究通过circRNA-seq及生物信息学分析发现，伏隔核circTmeff1-Tomoregulin-1调控网络在毒品潜伏心理渴求过程中可能发挥重要作用。本项目拟通过条件性位置偏爱及静脉自身给药建立潜伏心理渴求模型，结合化学遗传学技术过表达或敲减circTmeff1，明确其是否可以调节Tomoregulin-1表达并影响潜伏心理渴求过程；从circRNA-miRNA-mRNA和circRNA-蛋白互作角度研究circTmeff1调节Tomoregulin-1表达的网络机制，并阐明该网络对毒品潜伏心理渴求的影响及谷氨酸受体可塑性机制。项目的开展可丰富对毒品成瘾机制的认识，为复吸防治提供新的干预靶点。

Persistent drug craving is an important cause of relapse. As a key regulator, circRNA played an important role in neurological diseases such as Parkinson's disease and depression. However, the effect of circRNA on drug craving is not clear. The results from preliminary study by circRNA-seq techniques and bioformatics analysis indicated that circTmeff1-Tomoregulin-1 network in the nucleus accumbens has significant functions in drug craving. The present project will firstly establish the incubation of drug craving animal model by CPP and SA procedure and then over-express or knockdown circTmeff1 by chemical genetic techniques, which aims to clarify whether circTmeff1 could regulate the Tomoregulin-1 expression and influence the incubation of drug craving process. Furthermore, we will study the circRNA-miRNA-mRNA and circRNA-protein interaction to clarify the mechanism of circTmeff1-Tomoregulin-1 network. The influence of circTmeff1-Tomoregulin-1 network on the incubation of drug craving and underlying mechanisms including the plasticity of AMPA receptor will also be explored. The development of this project will enrich the knowledge of drug addiction and provide new intervention targets for the relapse medication.