The research team analyzed how cocaine use disorder impacts gene activity in the striatum, a brain region involved in motivation, reward, and habit formation. They found that cocaine use alters gene networks that control neurotransmission in two striatal brain regions, the nucleus accumbens (NAc) and the caudate nucleus (CN). The team likewise analyzed gene activity in mice that self-administered cocaine and found that many of the cocaine-related changes seen in humans were also present in these mice. Their analyses revealed that human gene modules governing brain plasticity are similarly altered by cocaine in a particular subtype of neuron in mice that respond to dopamine, the D1 medium spiny neurons (D1 MSNs). Together, these conserved molecular signatures indicate that key gene networks may be critical to the development of cocaine use disorder, and that animal models are valuable in studying how cocaine alters the human brain.