To investigate the influence of genetic background and sex on addiction, we conducted a study on the striatum of mice, a crucial brain structure linked to various substance abuse disorders, at the single-cell level. We utilized single-cell multi-omics technology to analyze the gene expression and chromatin accessibility of individual cells in the mice striatum. Overall design: Mouse striatum were from 8 inbred strains: A/J, C57BL/6J, 129S1/SvImJ, NOD/ShiLtJ, NZO/H1LtJ, CAST/EiJ, PWK/PhJ, and WSB/EiJ. A total of 32 striatum samples were divided in 4 batches, with each batch consisting of 4 male and 4 female samples, and each strain represented in each batch.