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The mechanisms by which lithium exerts these actions are poorly understood. Pre\u2010clinical and clinical evidence have implicated increased mesolimbic dopamine (<jats:styled-content style=\"fixed-case\">DA<\/jats:styled-content>) neurotransmission with mania. We used fast\u2010scan cyclic voltammetry to characterize changes in extracellular <jats:styled-content style=\"fixed-case\">DA<\/jats:styled-content> concentrations in the nucleus accumbens (<jats:styled-content style=\"fixed-case\">NA<\/jats:styled-content>c) core evoked by 20 and 60\u00a0Hz electrical stimulation of the ventral tegmental area (<jats:styled-content style=\"fixed-case\">VTA<\/jats:styled-content>) in C57<jats:styled-content style=\"fixed-case\">BL<\/jats:styled-content>6\/J mice treated either acutely or chronically with lithium. The effects of chronic lithium treatment on the availability of <jats:styled-content style=\"fixed-case\">DA<\/jats:styled-content> for release were assessed by depleting readily releasable <jats:styled-content style=\"fixed-case\">DA<\/jats:styled-content> using short inter\u2010train intervals, or administering <jats:italic>d<\/jats:italic>\u2010amphetamine acutely to mobilize readily releasable <jats:styled-content style=\"fixed-case\">DA<\/jats:styled-content>. Chronic, but not acute, lithium treatment decreased the amplitude of <jats:styled-content style=\"fixed-case\">DA<\/jats:styled-content> responses in the <jats:styled-content style=\"fixed-case\">NA<\/jats:styled-content>c following 60\u00a0Hz pulse train stimulation. Neither lithium treatment altered the kinetics of <jats:styled-content style=\"fixed-case\">DA<\/jats:styled-content> release or reuptake. Chronic treatment did not impact the progressive reduction in the amplitude of <jats:styled-content style=\"fixed-case\">DA<\/jats:styled-content> responses when, using 20 or 60\u00a0Hz pulse trains, the <jats:styled-content style=\"fixed-case\">VTA<\/jats:styled-content> was stimulated every 6\u00a0s to deplete <jats:styled-content style=\"fixed-case\">DA<\/jats:styled-content>. Specifically, the amplitude of <jats:styled-content style=\"fixed-case\">DA<\/jats:styled-content> responses to 60\u00a0Hz pulse trains was initially reduced compared to control mice, but by the fifth pulse train, there was no longer a treatment effect. However, chronic lithium treatment attenuated <jats:italic>d<\/jats:italic>\u2010amphetamine\u2010induced increases in <jats:styled-content style=\"fixed-case\">DA<\/jats:styled-content> responses to 20\u00a0Hz pulse trains stimulation. Our data suggest that long\u2010term administration of lithium may ameliorate mania phenotypes by normalizing the readily releasable <jats:styled-content style=\"fixed-case\">DA<\/jats:styled-content> pool in <jats:styled-content style=\"fixed-case\">VTA<\/jats:styled-content> axon terminals in the <jats:styled-content style=\"fixed-case\">NA<\/jats:styled-content>c.<\/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\/jnc13769-fig-0005-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p><jats:p><jats:bold>Read the Editorial Highlight<\/jats:bold> for this article on <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/dx.doi.org\/10.1111\/jnc.13846\">Page 520<\/jats:ext-link>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.13769","type":"journal-article","created":{"date-parts":[[2016,8,11]],"date-time":"2016-08-11T14:16:45Z","timestamp":1470925005000},"page":"576-585","source":"Crossref","is-referenced-by-count":23,"title":["Chronic lithium treatment rectifies maladaptive dopamine release in the nucleus accumbens"],"prefix":"10.1111","volume":"139","author":[{"given":"Adem","family":"Can","sequence":"first","affiliation":[{"name":"Department of Psychiatry University of Maryland School of Medicine Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Douglas O.","family":"Frost","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Maryland School of Medicine Baltimore Maryland USA"},{"name":"Department of Pharmacology University of Maryland School of Medicine Baltimore Maryland 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