Convergent abnormalities in striatal gene networks in human cocaine use disorder and mouse cocaine administration models

• DOI: 10.1126/sciadv.add8946
• Publication Date: 2023-05-15T18:06:21Z
• Authors: Philipp Mews; Ashley M. Cunningham; Joseph Scarpa; Aarthi Ramakrishnan; Emily M. Hicks; Sarah Bolnick; Susanna Garamszegi; Li Shen; Deborah C. Mash; Eric J. Nestler
• Keywords: Medium spiny neuron; Neurochemical

Cocaine use disorder (CUD) is an intractable syndrome, and rising overdose death rates represent a substantial public health crisis that exacts tremendous personal financial costs on patients society. Sharp increases in cocaine drive the urgent need for better mechanistic insight into this chronic relapsing brain currently lacks effective treatment options. To investigate transcriptomic changes involved, we conducted RNA sequencing two striatal regions are heavily implicated CUD, nucleus accumbens caudate nucleus, from men suffering CUD matched controls. Weighted gene coexpression analyses identified CUD-specific networks enriched ionotropic receptors linked to lowered neuroinflammation, contrasting proinflammatory responses found opioid disorder. Integration of comprehensive datasets mouse self-administration models revealed evolutionarily conserved implicate especially D1 medium spiny neurons as drivers cocaine-induced plasticity.