●Chronic use of illicit drugs impacts behavior, neuronal structure, electrophysiological properties, and gene expression in mutliple brain regions ● Cocaine self-administration significantly alters mitochondrial size in Nucleus Accumbens (NAc) medium spiny neurons ● Disrupting mitochondrial fission blunts behavioral responding for cocaine in a self-administration paradigm Here we examine gene expression in NAc and brain regions that provide inputs to NAc in mice that recieved an acute dose of cocaine or had undergone cocaine self-administration, focusing on mitochondrial-related gene ontology (GO) terms and predictive transcriptional regulation.