{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T05:10:33Z","timestamp":1772169033054,"version":"3.50.1"},"reference-count":74,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2015,1,23]],"date-time":"2015-01-23T00:00:00Z","timestamp":1421971200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns4:p>\n                    <ns4:bold>Rationale:<\/ns4:bold>\n                    Synaptic dopamine (DA) release induced by amphetamine or other experimental manipulations can displace [\n                    <ns4:sup>11<\/ns4:sup>\n                    C]raclopride (RAC*) from dopamine D2-like receptors. We hypothesized that exogenous levodopa might increase dopamine release at striatal synapses under some conditions but not others, allowing a more naturalistic assessment of presynaptic dopaminergic function. Presynaptic dopaminergic abnormalities have been reported in Tourette syndrome (TS).\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Objective:<\/ns4:bold>\n                    Test whether levodopa induces measurable synaptic DA release in healthy people at rest, and gather pilot data in TS.\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Methods:<\/ns4:bold>\n                    This double-blind crossover study used RAC* and positron emission tomography (PET) to measure synaptic dopamine release 4 times in each of 10 carbidopa-pretreated, neuroleptic-na\u00efve adults: before and during an infusion of levodopa on one day and placebo on another (in random order). Five subjects had TS and 5 were matched controls. RAC* binding potential (BP\n                    <ns4:sub>ND<\/ns4:sub>\n                    ) was quantified in predefined anatomical volumes of interest (VOIs). A separate analysis compared BP\n                    <ns4:sub>ND<\/ns4:sub>\n                    voxel by voxel over the entire brain.\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Results:<\/ns4:bold>\n                    DA release declined between the first and second scan of each day (p=0.012), including on the placebo day. Levodopa did not significantly reduce striatal RAC* binding and striatal binding did not differ significantly between TS and control groups. However, levodopa\u2019s effect on DA release differed significantly in a right midbrain region (p=0.002, corrected), where levodopa displaced RAC* by 59% in control subjects but\n                    <ns4:italic>increased<\/ns4:italic>\n                    BP\n                    <ns4:sub>ND<\/ns4:sub>\n                    by 74% in TS subjects.\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Discussion:<\/ns4:bold>\n                    Decreased DA release on the second scan of the day is consistent with the few previous studies with a similar design, and may indicate habituation to study procedures. We hypothesize that mesostriatal DA neurons fire relatively little while subjects rest, possibly explaining the non-significant effect of levodopa on striatal RAC* binding. The modest sample size argues for caution in interpreting the group difference in midbrain DA release with levodopa.\n                  <\/ns4:p>","DOI":"10.12688\/f1000research.5672.1","type":"journal-article","created":{"date-parts":[[2015,1,23]],"date-time":"2015-01-23T11:05:03Z","timestamp":1422011103000},"page":"23","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":18,"title":["Levodopa effects on [11C]raclopride binding in the resting human brain"],"prefix":"10.12688","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6921-9567","authenticated-orcid":false,"given":"Kevin J.","family":"Black","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marilyn 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Black","year":"2015","journal-title":"F1000Research."}],"container-title":["F1000Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/f1000research.com\/articles\/4-23\/v1\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/4-23\/v1\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/4-23\/v1\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,12,4]],"date-time":"2018-12-04T14:55:51Z","timestamp":1543935351000},"score":1,"resource":{"primary":{"URL":"https:\/\/f1000research.com\/articles\/4-23\/v1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,1,23]]},"references-count":74,"URL":"https:\/\/doi.org\/10.12688\/f1000research.5672.1","relation":{"has-review":[{"id-type":"doi","id":"10.5256\/f1000research.6062.r7601","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.6062.r7821","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.6062.r8060","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.6062.r8060","asserted-by":"object"},{"id-type":"doi","id":"10.5256\/f1000research.6062.r7821","asserted-by":"object"},{"id-type":"doi","id":"10.5256\/f1000research.6062.r7601","asserted-by":"object"}]},"ISSN":["2046-1402"],"issn-type":[{"value":"2046-1402","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,1,23]]},"assertion":[{"value":"Indexed","URL":"https:\/\/f1000research.com\/articles\/4-23\/v1#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.5256\/f1000research.6062.r7601, Marie Vidailhet, Department of Research of Technology and Development, H\u00f4pital Piti\u00e9 Salp\u00eatri\u00e8re, Paris, France, 17 Mar 2015, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/4-23\/v1#referee-response-7601","order":0,"name":"referee-response-7601","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.6062.r7821, W.R. Wayne Martin, Division of Neurology, University of Alberta, Edmonton, AB, Canada, 23 Mar 2015, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/4-23\/v1#referee-response-7821","order":1,"name":"referee-response-7821","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.6062.r8060, Lars Nyberg, Ume\u00e5 Center for Functional Brain Imaging, Ume\u00e5, Sweden, 23 Mar 2015, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/4-23\/v1#referee-response-8060","order":2,"name":"referee-response-8060","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Kevin J Black<\/b>; \n<i>Posted: 24 Mar 2015<\/i>; The authors thank Prof. Nyberg for the thoughtful review.&nbsp;The [\n<sup>11<\/sup>C]raclopride&nbsp;PET data were collected in 3D mode and reconstructed on the&nbsp;Siemens ECAT 961 scanner console using filtered backprojection (ramp filter), with attenuation measured before each emission scan using an external&nbsp;\n<sup>68<\/sup>Ge\/\n<sup>68<\/sup>Ga source.We agree with all the reviewers that the between-group comparison is useful primarily as pilot data because of the small group sizes.","URL":"https:\/\/f1000research.com\/articles\/4-23\/v1#referee-comment-1280","order":3,"name":"referee-comment-1280","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Kevin J Black<\/b>; \n<i>Posted: 23 Nov 2015<\/i>; A 2015 paper by Alakurtti and colleagues provides additional test-retest data on [\n<sup>11<\/sup>C]raclopride binding in thalamus and cortex.","URL":"https:\/\/f1000research.com\/articles\/4-23\/v1#article-response-1704","order":4,"name":"article-response-1704","label":"Article Comment","group":{"name":"article-comments","label":"Article Comments"}},{"value":"<b>Kevin J Black<\/b>; \n<i>Posted: 06 Jul 2015<\/i>; In reviewing structural MR studies of TS, I noticed that Garraux and colleagues (2006) reported increased gray matter volume&nbsp;in&nbsp;midbrain from&nbsp;a voxel-based morphometry study of symptomatic adults with TS. Their midbrain region included approximately STN\/VTA. Their finding needs replication and does not explain our results, but the identification of midbrain is interesting.","URL":"https:\/\/f1000research.com\/articles\/4-23\/v1#article-response-1446","order":5,"name":"article-response-1446","label":"Article Comment","group":{"name":"article-comments","label":"Article Comments"}},{"value":"<b>Kevin J Black<\/b>; \n<i>Posted: 04 Jun 2015<\/i>; Regarding the change in striatal [\n<sup>11<\/sup>C]raclopride binding from the first to the second scan on the placebo day (first paragraph of Discussion and Figures 5 and 6), I inadvertently omitted citations to two additional studies that also support the present results.&nbsp;Dewey \n<i>et al, <\/i>(1992) reported same-day test-retest values for striatal&nbsp;[\n<sup>11<\/sup>C]raclopride binding, using cerebellum as a reference region, in 6 experiments in 3 baboons. BP\n<sub>ND<\/sub>&nbsp;can be calculated from the values given in Table 1. Mean &plusmn; SD&nbsp;striatal&nbsp;BP\n<sub>ND<\/sub>&nbsp;was 2.012 &plusmn; 0.148&nbsp;on the first scan of the day and 2.180 &plusmn; 0.207&nbsp;on the second (mean change 8.4%, p=0.026 by paired t test using N=6, following the authors' analysis; alternatively, collapsing replicate measurements across days to the first- and second-scan means for each subject, 0.1&lt;p&lt;0.2 by unpaired t test, N=3).&nbsp;Wang \n<i>et al. <\/i>(1999, Table 1) reported test-retest results using a different paradigm in which 7 young healthy adult human volunteers were studied twice on each of two days, 1-2 weeks apart. The first scan on each day followed injection of a saline placebo, and the 2nd scan of each day followed injection of methylphenidate 0.5mg\/kg. Comparing the second to the first placebo scans,&nbsp;mean &plusmn; SD&nbsp;striatal&nbsp;BP\n<sub>ND<\/sub>&nbsp;increased from 2.768&nbsp;&plusmn; 0.437&nbsp;to 2.973&nbsp;&plusmn; 0.442 (mean change 7.8%, p=0.032 by paired t test).The study by&nbsp;Dewey and colleagues provides additional same-day test-retest data consistent with our results (compare also refs. 46 and 47 above). The Wang \n<i>et al.<\/i> study, which could have been cited with refs. 42-45 above, shows a similar test-retest increase in striatal [\n<sup>11<\/sup>C]raclopride&nbsp;binding over a period of 1-2 weeks, again consistent with a small decrease in synaptic dopamine concentration from the first to second scan.","URL":"https:\/\/f1000research.com\/articles\/4-23\/v1#article-response-1410","order":6,"name":"article-response-1410","label":"Article Comment","group":{"name":"article-comments","label":"Article Comments"}},{"value":"<b>Kevin J Black<\/b>; \n<i>Posted: 23 Mar 2015<\/i>; We thank Professors Vidailhet and Martin for their thoughtful comments.","URL":"https:\/\/f1000research.com\/articles\/4-23\/v1#article-response-1278","order":7,"name":"article-response-1278","label":"Article Comment","group":{"name":"article-comments","label":"Article Comments"}},{"value":"Data collection was supported by the Tourette Syndrome Association and manuscript preparation was supported in part by NIH grants K24 MH087913 and R21 MH098670. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":8,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Data associated with the article are available under the terms of the Creative Commons Zero \"No rights reserved\" data waiver (CC0 1.0 Public domain dedication).","order":0,"name":"copyright-info","label":"Copyright"}]}}