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We extended this line of investigation to examine behavioral sensitization, a commonly used model of cocaine\u2010induced behavioral and neuronal plasticity. Results indicated that male, but not female, offspring of cocaine\u2010taking sires showed deficits in the ability of repeated systemic cocaine injections to induce augmented locomotor activity. The reduced cocaine sensitization phenotype in male progeny was associated with changes in histone post\u2010translational modifications, epigenetic processes that regulate gene expression by controlling the accessibility of genes to transcriptional machinery, in the nucleus accumbens of first\u2010generation male progeny. Thus, five histone post\u2010translational modifications were significantly altered in the male progeny of cocaine\u2010exposed sires. In contrast, self\u2010administration of nicotine was unaltered in male and female offspring suggesting that the intergenerational effects of paternal cocaine taking may be drug\u2010specific. Interestingly, the reduced sensitivity to cocaine previously observed in the male offspring of cocaine\u2010taking sires dissipated in the grand\u2010offspring. Both male and female grand\u2010progeny of cocaine\u2010exposed sires showed unaltered cocaine\u2010induced behavioral sensitization and cocaine self\u2010administration. Taken together, these findings indicate that paternal cocaine taking produces changes in multiple cocaine addiction\u2010related behaviors in male progeny, which do not persist beyond the first generation of offspring. Moreover, the altered sensitivity to cocaine in first\u2010generation male progeny of cocaine\u2010sired male offspring was associated with epigenetic modifications in the nucleus accumbens, a nucleus that plays a critical role in cocaine\u2010associated behavioral plasticity.<\/jats:p>","DOI":"10.1111\/ejn.14310","type":"journal-article","created":{"date-parts":[[2018,12,19]],"date-time":"2018-12-19T07:04:59Z","timestamp":1545203099000},"page":"1115-1126","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Impaired cocaine\u2010induced behavioral plasticity in the male offspring of cocaine\u2010experienced sires"],"prefix":"10.1111","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4098-2497","authenticated-orcid":false,"given":"Mathieu E.","family":"Wimmer","sequence":"first","affiliation":[{"name":"Department of Psychology and Neuroscience Program College of Liberal Arts Temple University Philadelphia Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fair M.","family":"Vassoler","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences Cummings School of Veterinary Medicine Tufts University Grafton Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samantha L.","family":"White","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Center for Neurobiology and Behavior Perelman School of Medicine at the University of Pennsylvania Philadelphia Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heath D.","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Center for Neurobiology and Behavior Perelman School of Medicine at the University of Pennsylvania Philadelphia Pennsylvania"},{"name":"Department of Biobehavioral Health Sciences School of Nursing University of Pennsylvania Philadelphia Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simone","family":"Sidoli","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biophysics Epigenetics Institute Perelman School of Medicine at the University of Pennsylvania Philadelphia Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yumiao","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biophysics Epigenetics Institute Perelman School of Medicine at the University of Pennsylvania Philadelphia Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin A.","family":"Garcia","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biophysics Epigenetics Institute Perelman School of Medicine at the University of Pennsylvania Philadelphia Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R. 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