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Stereotypies are also evoked by psychomotor stimulants such as amphetamine. The acquisition of motor sequences is paralleled by changes in activity patterns in the striatum, and stereotypies have been linked to abnormal plasticity in these reinforcement\u2010related circuits. Here, we designed experiments in mice to identify transcriptomic changes that underlie striatal plasticity occurring alongside the development of drug\u2010induced stereotypic behavior. We identified three schedules of amphetamine treatment inducing different degrees of stereotypy and used bulk RNAseq to compare striatal gene expression changes among groups of mice treated with the different drug\u2010dose schedules and vehicle\u2010treated, cage\u2010mate controls. Mice were identified as na\u00efve, sensitized, or tolerant to drug\u2010induced stereotypy. All drug\u2010treated groups exhibited expression changes in genes that encode members of the extracellular signal\u2010regulated kinase (ERK) cascades known to regulate psychomotor stimulant responses. In the sensitized group with the most prolonged stereotypy, we found dysregulation of 20 genes that were not changed in other groups. Gene set enrichment analysis indicated highly significant overlap with genes regulated by neuregulin 1 (Nrg1). Nrg1 is known to be a schizophrenia and autism susceptibility gene that encodes a ligand for Erb\u2010B receptors, which are involved in neuronal migration, myelination, and cell survival, including that of dopamine\u2010containing neurons. Stimulant abuse is a risk factor for schizophrenia onset, and these two disorders share behavioral stereotypy phenotypes. Our results raise the possibility that drug\u2010induced sensitization of the Nrg1 signaling pathway might underlie these links.<\/jats:p>","DOI":"10.1111\/ejn.15116","type":"journal-article","created":{"date-parts":[[2021,3,24]],"date-time":"2021-03-24T01:46:06Z","timestamp":1616550366000},"page":"2450-2468","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Striatal transcriptome changes linked to drug\u2010induced repetitive behaviors"],"prefix":"10.1111","volume":"53","author":[{"given":"Jill R.","family":"Crittenden","sequence":"first","affiliation":[{"name":"McGovern Institute for Brain Research The Massachusetts Institute of Technology Cambridge MA USA"},{"name":"Department of Brain and Cognitive Sciences The Massachusetts Institute of Technology Cambridge MA USA"},{"name":"Institute for Integrative Cancer Research The Massachusetts Institute of Technology Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa A.","family":"Gipson","sequence":"additional","affiliation":[{"name":"Institute for Integrative Cancer Research The Massachusetts Institute of Technology Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne C.","family":"Smith","sequence":"additional","affiliation":[{"name":"Evelyn F. 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