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This study used arterial spin labeling (ASL) to investigate the effects of a single low dose of amisulpride, a selective DA antagonist, on cerebral blood flow (CBF) in MDD patients and healthy volunteers (HVs). In a double-blind, placebo-controlled, randomized, parallel-group design, participants received either 100\u2009mg amisulpride or placebo.\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u2009111 participants (MDD:\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200957; HV:\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200954) were included in the final analysis and group differences were assessed in core regions of the reward network, particularly the ventral striatum. Individual CBF values were analyzed in relation to self-reported anhedonia and depression severity. Amisulpride was associated with higher perfusion in the ventral striatum compared to placebo in both HVs and MDD patients, consistent with enhanced dopaminergic activity in this region. No significant CBF changes were observed in other areas of the reward network. Ventral striatal perfusion was significantly associated with self-reported anhedonia. Exploratory whole-brain analyses revealed higher CBF in the right frontal operculum in MDD patients compared to HVs under placebo, but not under amisulpride. In the placebo group, both anhedonia and depression severity were associated with CBF in the right frontal operculum; these associations were absent following amisulpride administration. In conclusion, we provide initial evidence of region-specific effects of amisulpride administration on CBF that are consistent with modulation of dopaminergic signaling. Increased perfusion in the ventral striatum suggests a potential dopaminergic mechanism relevant to anhedonia. These findings underscore the ventral striatum\u2019s role in reward processing and support its involvement in the pathophysiology of anhedonia across clinical and non-clinical populations.\n                  <\/jats:p>","DOI":"10.1038\/s41386-026-02471-6","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T23:32:12Z","timestamp":1782430332000},"page":"1808-1815","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Investigating the effect of increased dopamine signaling on cerebral blood flow in Major Depressive Disorder: a double-blind randomized placebo-controlled study"],"prefix":"10.1038","volume":"51","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1185-1789","authenticated-orcid":false,"given":"Matti","family":"G\u00e4rtner","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9747-5015","authenticated-orcid":false,"given":"Marvin S.","family":"Meiering","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Weigner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5793-7636","authenticated-orcid":false,"given":"Moritz","family":"Hempel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3355-7724","authenticated-orcid":false,"given":"Rebecca","family":"Gruzman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa","family":"Carstens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7552-4082","authenticated-orcid":false,"given":"Christian","family":"Keicher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maarten","family":"Mennes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian F.","family":"Beckmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerd","family":"Luippold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9648-3831","authenticated-orcid":false,"given":"Sigurd D.","family":"S\u00fcssmuth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margot","family":"Popp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Wunder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Grimm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,26]]},"reference":[{"key":"2471_CR1","doi-asserted-by":"crossref","unstructured":"Shankman SA, Katz AC, DeLizza AA, Sarapas C, Gorka SM, Campbell ML. 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