OBJECTIVE Cue-induced drug craving progressively increase after prolong abstinence in animal and human beings.A behavioral phenomenon termed incubation of drug craving is considered as a key reason for drug relapse,bu...OBJECTIVE Cue-induced drug craving progressively increase after prolong abstinence in animal and human beings.A behavioral phenomenon termed incubation of drug craving is considered as a key reason for drug relapse,but the transcriptional mechanisms that contribute to this incubation are unknown.It has been demonstrated that circular RNAs(circR NAs),act as miR NA sponges,play important roles in the regulation of gene expression and the pathogenesis of disease.The present study aims to explore the transcriptional profiles associated with incubation of morphine craving in nucleus accumbens(NAc),an important brain area previously implicated in drug seeking.METHODS The animal model of the incubation of drug craving was induced by CPP paradigms with six morphine(5 mg·kg-1) injections and 14 d drug abstinence in mice.The brain tissues of NAc were collected after the behavioral tests for circRNA-sequencing by Illumina Hiseq X sequencer.We identified differentially expressed genes(DEGs) by qRT-PCR and used bioinformatics methods for further function analysis.RESULTS The progressive increase of CPP scores during the 14 d drug abstinence indicated the establishment of animal model.The data of circRNA-sequencing reported that 16 circRNAs were significantly altered after 28 d drug abstinence in NAc of morphine treated mice(FC≥2 and P<0.05).Among those circRNAs,9 were significantly up-regulated,while 7 were down-regulated.Furthermore,we subsequently tested circRNAs expression using quantitative real-time PCR,and the consistent data were obtained.The results of KEGG pathway analysis indicated that these genes were enriched for several biological processes,including RNA transport,protein ubiquitination and histone methylation,etc.CONCLUSION These findings provide a unique resource of gene expression data for future studies examining transcriptional mechanisms in NAc that mediate opioids seeking after prolonged withdrawal.展开更多
基金Natural Science Foundation of Hebei Province(H2018206166)National Natural Science Foundation of China (81871524).
文摘OBJECTIVE Cue-induced drug craving progressively increase after prolong abstinence in animal and human beings.A behavioral phenomenon termed incubation of drug craving is considered as a key reason for drug relapse,but the transcriptional mechanisms that contribute to this incubation are unknown.It has been demonstrated that circular RNAs(circR NAs),act as miR NA sponges,play important roles in the regulation of gene expression and the pathogenesis of disease.The present study aims to explore the transcriptional profiles associated with incubation of morphine craving in nucleus accumbens(NAc),an important brain area previously implicated in drug seeking.METHODS The animal model of the incubation of drug craving was induced by CPP paradigms with six morphine(5 mg·kg-1) injections and 14 d drug abstinence in mice.The brain tissues of NAc were collected after the behavioral tests for circRNA-sequencing by Illumina Hiseq X sequencer.We identified differentially expressed genes(DEGs) by qRT-PCR and used bioinformatics methods for further function analysis.RESULTS The progressive increase of CPP scores during the 14 d drug abstinence indicated the establishment of animal model.The data of circRNA-sequencing reported that 16 circRNAs were significantly altered after 28 d drug abstinence in NAc of morphine treated mice(FC≥2 and P<0.05).Among those circRNAs,9 were significantly up-regulated,while 7 were down-regulated.Furthermore,we subsequently tested circRNAs expression using quantitative real-time PCR,and the consistent data were obtained.The results of KEGG pathway analysis indicated that these genes were enriched for several biological processes,including RNA transport,protein ubiquitination and histone methylation,etc.CONCLUSION These findings provide a unique resource of gene expression data for future studies examining transcriptional mechanisms in NAc that mediate opioids seeking after prolonged withdrawal.
