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Positron emission tomography (PET) with the D2\/D3 receptor radioligand [\n                    <jats:sup>11<\/jats:sup>\n                    C]raclopride remains the most widely used method for indirectly quantifying striatal dopamine release in vivo. However, no previous meta-analysis has studied the relative magnitude and regional distribution of dopamine release across different interventions or cognitive interventions overall. To address this gap, in this meta-analysis of 92 [\n                    <jats:sup>11<\/jats:sup>\n                    C]raclopride PET studies (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20091640), we compared the magnitude and regional distribution of dopamine release induced by amphetamine, methylphenidate, ketamine, alcohol, and cognitive challenges with and without reward. Amphetamine induced approximately four-fold greater dopamine release than cognitive challenges (10.9 vs. 2.7%, p\u2009&lt;\u20090.001), and approximately twice that of alcohol (4.8%, p\u2009&lt;\u20090.001), with effects comparable to methylphenidate (11.5%) and slightly greater than ketamine (9.8%). Psychostimulant-induced increase in synaptic dopamine was greater in putamen and ventral striatum than in caudate, whereas alcohol preferentially engaged ventral striatum. Dopamine release did not differ between rewarded and non-rewarded cognitive tasks in the ventral striatum (p\u2009&gt;\u20090.14) or overall striatum (p\u2009&gt;\u20090.10). Methylphenidate-induced increases in synaptic dopamine appeared to attenuate with advancing age, whereas cognitive challenges were associated with greater dopamine release in older individuals. These findings demonstrate that individual pharmacological and cognitive interventions differ markedly in both magnitude and regional pattern of dopamine release. They also suggest that [\u00b9\u00b9C]raclopride PET may have limited sensitivity for distinguishing reward-related from non-reward-related dopamine release. These findings have implications for the design and interpretation of future neuroimaging studies of dopaminergic function in health and disease.\n                  <\/jats:p>","DOI":"10.1038\/s41380-026-03826-7","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T16:57:06Z","timestamp":1788541026000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Pharmacological and non-pharmacological modulation of striatal dopamine release: a meta-analysis of [11C]raclopride PET studies"],"prefix":"10.1038","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1947-712X","authenticated-orcid":false,"given":"Mikael","family":"Eklund","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eman","family":"Hassanain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tero","family":"Vahlberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3457-9415","authenticated-orcid":false,"given":"Juho","family":"Joutsa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3446-7093","authenticated-orcid":false,"given":"Valtteri","family":"Kaasinen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,4]]},"reference":[{"key":"3826_CR1","doi-asserted-by":"publisher","first-page":"735","DOI":"10.3390\/cells10040735","volume":"10","author":"L Speranza","year":"2021","unstructured":"Speranza L, di Porzio U, Viggiano D, de Donato A, Volpicelli F. 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E.H. and T.V. declare that they have no conflict of interest. J.J. has received research funding from the Research Council of Finland, Finnish Medical Foundation, Sigrid Juselius Foundation, Signe & Ane Gyllenberg\u2019s Foundation, P\u00e4ivikki and Sakari Sohlberg\u2019s Foundation, Finnish Parkinson Foundation, Turku University Hospital (VTR), Dystonia Medical Research Foundation, Dysphonia international, and Finnish Foundation for Alcohol Studies, lecturer honoraria from Insightec, Addiktum, Nordic Infucare, Lundbeck and Novartis, conference travel support from Abbvie, Abbott and Insightec, and consultancy fees from Summaryx, Adamant Health and TEVA Finland; acts as an advisory board member for TEVA Finland; and owns stock of Neurologic Finland and Suomen Neurolaboratorio. V.K. has received research funding from the Finnish Parkinson Foundation, the Finnish Cultural Foundation, the Turku University Foundation, the P\u00e4ivikki and Sakari Sohlberg Foundation and Turku University Hospital (VTR-funds). He has received speaker honoraria from Lundbeck, Bial, Abbvie, Nordic Infucare AB, Orion Pharma, Eisai, and Teva, and travel support from Nordic Infucare AB, and acts as an advisory board member for Abbvie, Nordic Infucare AB and Orion Pharma.","order":1,"name":"Ethics","label":"Competing interest","group":{"name":"EthicsHeading","label":"Ethics"}},{"value":"This meta-analysis used previously published data and did not involve new recruitment of human participants or collection of identifiable individual-level data; therefore, ethics committee approval and new informed consent were not required.","order":2,"name":"Ethics","label":"Ethics declaration","group":{"name":"EthicsHeading","label":"Ethics"}}]}}