Differential expression of miR-1249-3p and miR-34b-5p between vulnerable and resilient phenotypes of cocaine addiction

Abstract

Cocaine addiction is a complex brain disorder involving long-term alterations that leadto loss of control over drug seeking. The transition from recreational use to pathologi-cal consumption is different in each individual, depending on the interaction betweenenvironmental and genetic factors. Epigenetic mechanisms are ideal candidates tostudy psychiatric disorders triggered by these interactions, maintaining persistentmalfunctions in specific brain regions. Here we aim to study brain-region-specific epi-genetic signatures following exposure to cocaine in a mouse model of addiction tothis drug. Extreme subpopulations of vulnerable and resilient phenotypes wereselected to identify miRNA signatures for differential vulnerability to cocaine addic-tion. We used an operant model of intravenous cocaine self-administration to evalu-ate addictive-like behaviour in rodents based on the Diagnostic and StatisticalManual of Mental Disorders Fifth Edition criteria to diagnose substance use disor-ders. After cocaine self-administration, we performed miRNA profiling to comparetwo extreme subpopulations of mice classified as resilient and vulnerable to cocaineaddiction. We found that mmu-miR-34b-5p was downregulated in the nucleusaccumbens of vulnerable mice with high motivation for cocaine. On the other hand,mmu-miR-1249-3p was downregulated on vulnerable mice with high levels of motordisinhibition. The elucidation of the epigenetic profile related to vulnerability to cocaine addiction is expected to help find novel biomarkers that could facilitate theinterventions to battle this devastating disorder.