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Here, we sought to determine whether this phenotype extended to another psychostimulant, methamphetamine (meth). Sires self-administered meth or cocaine or received yoked-saline infusions for 60 days, after which they were mated to na\u00efve females. Some behaviors previously altered in cocaine-sired male rats, including object memory and anxiety-like behavior, were not influenced by paternal meth taking. In contrast to cocaine resistance in cocaine-sired male rats, meth-sired male offspring demonstrated increased susceptibility to meth taking, with no effect in females. Single nuclei RNA- and ATAC-sequencing of the nucleus accumbens was used to identify molecular drivers of phenotypes in cocaine- and meth-sired offspring. Sequencing results revealed unique profiles of gene expression and open chromatin in offspring nucleus accumbens. Differential gene expression in cocaine-resistant, cocaine-sired offspring and meth-susceptible, meth-sired offspring illuminates potential novel treatment targets for psychostimulant use disorders.<\/jats:p>","DOI":"10.1038\/s41386-026-02520-0","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T13:26:11Z","timestamp":1786541171000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Paternal epigenetic inheritance increases susceptibility to methamphetamine taking"],"prefix":"10.1038","author":[{"given":"Sarah E.","family":"Swinford-Jackson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6331-5980","authenticated-orcid":false,"given":"BaDoi N.","family":"Phan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azadeh","family":"Jadali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mateo","family":"Sarmiento Bustamante","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharvari","family":"Mankame","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha J.","family":"Worobey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8940-2476","authenticated-orcid":false,"given":"Tyler J.","family":"Sacko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominick","family":"Gangemi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixiao","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas R.","family":"Pfenning","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelvin Y.","family":"Kwan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald P.","family":"Hart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. 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