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CART neurons of the lateral hypothalamus (LH) send afferents to the ventral tegmental area (VTA) and paraventricular thalamic nucleus (PVT) and these nuclei, in turn, send secondary projections to nucleus accumbens. We try to dissect the precise sites of CART\u2019s action in these circuits in promoting reward. Rats were implanted with bipolar electrode targeted at the lateral hypothalamus\u2010medial forebrain bundle (LH\u2010MFB) and trained to press the lever through intracranial self\u2010stimulation (ICSS) protocol. CART (55\u2013102) administered directly into posterior VTA (pVTA) or PVT of the conditioned rats significantly increased the number of lever presses, indicating reward\u2010promoting activity of the peptide. Concomitant increase in dopamine (DA) and 3, 4\u2010dihydroxyphenylacetic acid (DOPAC) efflux was noted in the microdialysate collected from the nucleus accumbens shell (AcbSh). On the other hand, immunoneutralization of endogenous CART with CART antibodies injected directly in the pVTA or PVT reduced the lever press activity as well as DA and DOPAC efflux in the AcbSh. Injection of CART (1\u201339) in pVTA or PVT was ineffective. We suggest that CART cells in the LH\u2010MFB area send afferents to (a) pVTA and influence dopaminergic neurons projecting to AcbSh and (b) PVT, from where the secondary neurons may feed into the AcbSh. Excitation of the CARTergic pathway to the pVTA as well as the PVT seems to promote DA release in the AcbSh and contribute to the generation of reward.<\/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\/jnc15479-fig-0007-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.15479","type":"journal-article","created":{"date-parts":[[2021,7,21]],"date-time":"2021-07-21T09:02:20Z","timestamp":1626858140000},"page":"1172-1185","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Neuropeptide CART modulates dopamine turnover in the nucleus accumbens: Insights into the anatomy of rewarding circuits"],"prefix":"10.1111","volume":"158","author":[{"given":"Sanjay N.","family":"Awathale","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences Rashtrasant Tukadoji Maharaj Nagpur University Nagpur India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit G.","family":"Choudhary","sequence":"additional","affiliation":[{"name":"Indian Institute of Science Education and Research (IISER) Pune India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nishikant K.","family":"Subhedar","sequence":"additional","affiliation":[{"name":"Indian Institute of Science Education and Research (IISER) Pune India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5212-5719","authenticated-orcid":false,"given":"Dadasaheb M.","family":"Kokare","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Rashtrasant Tukadoji Maharaj Nagpur University Nagpur India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,8,6]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-008-7521-8"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2009.09.106"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2020.108791"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.07.015"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-4328(96)00129-5"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(97)01373-5"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-10-03864.2000"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2007.03.021"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0509607102"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2012.02.036"},{"key":"e_1_2_11_12_1","first-page":"1313","article-title":"CART neurons in the lateral hypothalamus communicate with the nucleus accumbens shell via glutamatergic neurons in paraventricular thalamic nucleus to modulate reward behavior","volume":"223","author":"Choudhary A. 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