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These neurons are important targets for metabolic hormones such as leptin, glucagon\u2010like peptide\u20101, ghrelin and insulin. Insulin receptors are located on dopamine neurons in the ventral tegmental area (<jats:styled-content style=\"fixed-case\">VTA<\/jats:styled-content>) and we have previously demonstrated that insulin induces long\u2010term depression of excitatory synapses onto <jats:styled-content style=\"fixed-case\">VTA<\/jats:styled-content> dopamine neurons. While insulin can decrease dopamine concentration in somatodendritic regions, it can increase dopamine in striatal slices. Whether insulin directly targets the <jats:styled-content style=\"fixed-case\">VTA<\/jats:styled-content> to alter dopamine release in projection areas, such as the nucleus accumbens (<jats:styled-content style=\"fixed-case\">NA<\/jats:styled-content>c), remains unknown. The main goal of the present experiments was to examine <jats:styled-content style=\"fixed-case\">NA<\/jats:styled-content>c dopamine concentration following <jats:styled-content style=\"fixed-case\">VTA<\/jats:styled-content> administration of insulin. Using <jats:italic>in\u00a0vivo<\/jats:italic> FSCV to detect rapid fluctuations in dopamine concentration, we showed that intra\u2010<jats:styled-content style=\"fixed-case\">VTA<\/jats:styled-content> insulin via action at insulin receptors reduced pedunculopontine nucleus\u2010evoked dopamine release in the <jats:styled-content style=\"fixed-case\">NA<\/jats:styled-content>c. Furthermore, intra\u2010<jats:styled-content style=\"fixed-case\">VTA<\/jats:styled-content> insulin reduced cocaine\u2010potentiated <jats:styled-content style=\"fixed-case\">NA<\/jats:styled-content>c dopamine. Finally, intra\u2010<jats:styled-content style=\"fixed-case\">VTA<\/jats:styled-content> or intranasal insulin decreased locomotor responses to cocaine, an effect blocked by an intra\u2010<jats:styled-content style=\"fixed-case\">VTA<\/jats:styled-content> administered insulin receptor antagonist. Together, these data demonstrate that mesolimbic dopaminergic projections are important targets of the metabolic hormone, insulin.<\/jats:p>","DOI":"10.1111\/ejn.14291","type":"journal-article","created":{"date-parts":[[2018,11,24]],"date-time":"2018-11-24T16:15:55Z","timestamp":1543076155000},"page":"2146-2155","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Insulin in the ventral tegmental area reduces cocaine\u2010evoked dopamine in the nucleus accumbens <i>in\u00a0vivo<\/i>"],"prefix":"10.1111","volume":"50","author":[{"given":"Lindsay","family":"Naef","sequence":"first","affiliation":[{"name":"Department of Physiology &amp; Pharmacology Cumming School of Medicine Hotchkiss Brain Institute University of Calgary Calgary Alberta T2N 4N1 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3970-6580","authenticated-orcid":false,"given":"Lauren","family":"Seabrook","sequence":"additional","affiliation":[{"name":"Department of Physiology &amp; Pharmacology Cumming School of Medicine Hotchkiss Brain Institute University of Calgary Calgary Alberta T2N 4N1 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeff","family":"Hsiao","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Pharmacology and Therapeutics University of British Columbia Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Calvin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Pharmacology and Therapeutics University of British Columbia Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7546-5687","authenticated-orcid":false,"given":"Stephanie L.","family":"Borgland","sequence":"additional","affiliation":[{"name":"Department of Physiology &amp; Pharmacology Cumming School of Medicine Hotchkiss Brain Institute University of Calgary Calgary Alberta T2N 4N1 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,12,11]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI29867"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2011-1443"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1001-08.2008"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0196-9781(98)00018-7"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(98)00583-1"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2011.01.020"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI99366"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1703-16.2016"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2011.02.028"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/jps.21924"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.85.14.5274"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2014.157"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-010-2048-8"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(02)04087-8"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.physbeh.2006.10.008"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.90334.2008"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1103"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.physbeh.2016.11.021"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.physbeh.2017.03.019"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2006.09.006"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.1995.tb00650.x"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2009-1677"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2016.234"},{"key":"e_1_2_10_25_1","first-page":"4440","article-title":"Intranasal administration of CNS therapeutics to awake mice","volume":"74","author":"Hanson L. 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