Alterations of RNAs in the insula related to cocaine-induced condition place preference in adolescent mice

Abstract

Cocaine as a highly addictive psychostimulant can cause changes in the body at the cellular and molecular levels over a long period of time. It reminds us that cocaine may have a potential role in post-transcriptional regulation, but the alteration of insula-expression profile in adolescent cocaine use disorder (CUD) has not been reported. To reveal the mechanisms underlying the post-transcriptional regulation of cocaine, we investigate the transcriptome in the insula of cocaine-induced mice based on high-throughput strand-specific RNA sequencing. We analyzed the alterations of messenger RNA (mRNA) expression profile in the insula of cocaine-induced condition place preference (CPP) mice and then correlated it with microRNAs to reveal their involvement in the formation of cocaine-induced CPP. In this study, a total of 27786 genes were identified, 5750 new genes (novel expressed transcripts of unannotated in the reference genome) were discovered, among which 1,205 were annotated functionally. A total of 198 differentially expressed genes (DEG) that functioned in synaptic transmission, cholinergic, developmental process, neurotransmitter metabolic process, drug catabolism, cellular response to drug, MAP kinase activity, ceramidase activity, and drug resistance were significantly enriched. Further analysis showed that 26045 mRNAs formed 45,208 network-relationship pairs with 1770 microRNAs. In the current study, our work was the first to reveal that alterations of RNAs in the insula, as a core brain region of the neural circuits of interoception, were involved in the process of cocaine-induced CPP of adolescent mice. These findings enrich the biology and expand the molecular regulatory network related to adolescence CUD. They provided the possibility that some DEGs may be used as novel biomarkers for the diagnosis or evaluation of substance use disorder, and also provided clues for elucidating the neurobiological mechanism of substance use disorder.