Study of brain specific miRNAs in cocaine addicted compulsive behavior Pohang University of Science and Technology

Abstract

Drug addiction is a chronic disorder of the brain's reward system that results in the compulsive seeking and use of drugs, despite the negative consequences that may arise and alter the brain's reward circuitry, which involves the neurotransmitter dopamine. So far, the neural circuitry and cell-specific mechanisms altered by cocaine have been studied, but the mechanisms of drug addiction induced by cocaine intake have been largely unresolved. MicroRNAs are a class of small, non-coding RNAs consisting of 21–23 nucleotides, and they serve as critical modulators of diverse cellular physiological pathways. Emerging evidence suggests that miRNAs play crucial roles in the rewiring of brain reward circuits following drug exposure, which is thought to underlie the development of addiction. Here, we report that microRNAs could be involved in cocaine addiction by utilizing a mouse model of cocaine self- administration. Using a cocaine self-administration mouse model, we divided mice into a compulsive behavior group (approximately 29%) and a non-compulsive behavior group (approximately 71%) in response to cocaine. Profiling of the selected miRNAs showed that the expression of miRNA-134-5p, which is involved in dendrite size, was significantly increased in the VTA of mice with compulsive behavior. Although the effect of a miRNA-134-5p-specific sponge virus administered to reduce miRNA-134-5p expression could not be confirmed, miRNA-134-5p overexpression in the VTA increased the proportion of mice exhibiting compulsive behavior (64%) in response to cocaine. These results suggest that miRNA-134-5p may be an effective target for treating compulsive behavior in response to cocaine.