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Frontal cortex and fronto\u2010striatal networks are implicated in working memory and these circuits rely on dopamine for optimal performance. Here, we aimed to determine if chronic Mn exposure alters <jats:italic>in\u00a0vivo<\/jats:italic> dopamine release (<jats:styled-content style=\"fixed-case\">DAR<\/jats:styled-content>) in the frontal cortex of non\u2010human primates. We used [<jats:sup>11<\/jats:sup>C]\u2010<jats:styled-content style=\"fixed-case\">FLB<\/jats:styled-content>457 positron emission tomography with amphetamine challenge to measure <jats:styled-content style=\"fixed-case\">DAR<\/jats:styled-content> in <jats:italic>Cynomolgus macaques<\/jats:italic>. Animals received [<jats:sup>11<\/jats:sup>C]\u2010<jats:styled-content style=\"fixed-case\">FLB<\/jats:styled-content>457 positron emission tomography scans with and without amphetamine challenge prior to Mn exposure (baseline), at different time points during the Mn exposure period, and after 10\u00a0months of Mn exposure cessation. Four of six Mn\u2010exposed animals expressed significant impairment of frontal cortex <jats:italic>in\u00a0vivo <\/jats:italic><jats:styled-content style=\"fixed-case\">DAR<\/jats:styled-content> relative to baseline. One Mn animal had no change in <jats:styled-content style=\"fixed-case\">DAR<\/jats:styled-content> and another Mn animal expressed increased <jats:styled-content style=\"fixed-case\">DAR<\/jats:styled-content> relative to baseline. In the reversal studies, one Mn\u2010exposed animal exhibited complete recovery of <jats:styled-content style=\"fixed-case\">DAR<\/jats:styled-content> while the second animal had partial recovery. In both animals, frontal cortex Mn concentrations normalized after 10\u00a0months of exposure cessation based on T1\u2010weighted magnetic resonance imaging. D1\u2010dopamine receptor (D1R) autoradiography in frontal cortex tissue indicates that Mn animals that experienced cessation of Mn exposure expressed D1R levels that were approximately 50% lower than Mn animals that did not experience cessation of Mn exposure or control animals. The present study provides evidence of Mn\u2010induced alterations in frontal cortex <jats:styled-content style=\"fixed-case\">DAR<\/jats:styled-content> and D1R that may be associated with working memory and attention deficits observed in Mn\u2010exposed subjects.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc14681-fig-0005-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.14681","type":"journal-article","created":{"date-parts":[[2019,2,5]],"date-time":"2019-02-05T16:30:52Z","timestamp":1549384252000},"page":"188-201","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["<scp>PET<\/scp> imaging of dopamine release in the frontal cortex of manganese\u2010exposed non\u2010human primates"],"prefix":"10.1111","volume":"150","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5376-6347","authenticated-orcid":false,"given":"Tomas R.","family":"Guilarte","sequence":"first","affiliation":[{"name":"Department of Environmental Health Sciences Robert Stempel College of Public Health and Social Work Florida International University Miami Florida USA"},{"name":"Department of Radiology Johns Hopkins Medical Institutions Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chien\u2010Lin","family":"Yeh","sequence":"additional","affiliation":[{"name":"Department of Radiology and Imaging Sciences Indiana University School of Medicine Indianapolis Indiana USA"},{"name":"School of Health Sciences Purdue University West Lafayette Indiana USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer L.","family":"McGlothan","sequence":"additional","affiliation":[{"name":"Department of Environmental Health Sciences Robert Stempel College of Public Health and Social Work Florida International University Miami Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan","family":"Perez","sequence":"additional","affiliation":[{"name":"Department of Environmental Health Sciences Robert Stempel College of Public Health and Social Work Florida International University Miami Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paige","family":"Finley","sequence":"additional","affiliation":[{"name":"Department of Radiology Johns Hopkins Medical Institutions Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yun","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Radiology Johns Hopkins Medical Institutions Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dean F.","family":"Wong","sequence":"additional","affiliation":[{"name":"Department of Radiology Johns Hopkins Medical Institutions Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulrike","family":"Dydak","sequence":"additional","affiliation":[{"name":"Department of Radiology and Imaging Sciences Indiana University School of Medicine Indianapolis Indiana USA"},{"name":"School of Health Sciences Purdue University West Lafayette Indiana USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jay S.","family":"Schneider","sequence":"additional","affiliation":[{"name":"Department of Pathology, Anatomy &amp; 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