{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,14]],"date-time":"2025-02-14T05:29:36Z","timestamp":1739510976831,"version":"3.37.0"},"reference-count":69,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2009,12,8]],"date-time":"2009-12-08T00:00:00Z","timestamp":1260230400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Neuroscience Research"],"published-print":{"date-parts":[[2010,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The serotonergic (5\u2010hydroxytryptamine; 5\u2010HT) dysfunction found in depression may affect not only brain function (mood) but also cerebrovascular control. Similar, but possibly occult, disturbances may also be induced by 3,4\u2010methylenedioxymethamphetamine\u2010induced neurotoxicty (MDMA, or \u201cecstasy\u201d). Acute tryptophan depletion (ATD) is widely used to identify vulnerability to depression, and we hypothesized that repeated MDMA administration would increase the sensitivity of rats to this acute serotonergic challenge. In this study, male Wistar rats were injected with MDMA (20 mg \u00b7 kg<jats:sup>\u22121<\/jats:sup>, twice daily for 4 days) and challenged 3 weeks later with ATD, induced by intragastric administration of a nutritional mixture with tryptophan (TRP) removed. Cerebral metabolism (CMRG) and blood flow (CBF) were measured in parallel groups of animals following ATD by using quantitative [<jats:sup>14<\/jats:sup>C]2\u2010deoxyglucose and [<jats:sup>14<\/jats:sup>C]iodoantipyrine autoradiographic techniques, respectively. A significant reduction in paroxetine binding to 5\u2010HT transporter sites in MDMA\u2010treated rats indicated 5HT terminal depletion, whereas the plasma TRP\/sum large neutral amino acids ratio was reduced by 40% following ATD. Under all experimental conditions, the normal close correlation between CBF and metabolic demand was maintained. However, a global analysis of all brain regions revealed a significant decrease in the overall ratio of CBF to CMRG after ATD in control animals, whereas a higher ratio was observed after ATD in the MDMA\u2010treated group. This increase in blood flow relative to cerebral metabolism suggests an ATD\u2010induced loss of cerebrovascular tone in MDMA\u2010treated animals that could have pathophysiological consequences and might conceivably contribute to the behavioral dysfunction of depression. \u00a9 2009 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jnr.22308","type":"journal-article","created":{"date-parts":[[2009,12,8]],"date-time":"2009-12-08T22:13:27Z","timestamp":1260310407000},"page":"1557-1568","source":"Crossref","is-referenced-by-count":9,"title":["Acute tryptophan depletion potentiates 3,4\u2010methylenedioxymethamphetamine\u2010induced cerebrovascular hyperperfusion in adult male wistar rats"],"prefix":"10.1002","volume":"88","author":[{"given":"Eva L.","family":"van Donkelaar","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul A.T.","family":"Kelly","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neil","family":"Dawson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arjan","family":"Blokland","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos","family":"Prickaerts","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harry W.M.","family":"Steinbusch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linda","family":"Ferrington","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,12,8]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2005.12.010"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-004-1787-9"},{"key":"e_1_2_5_4_1","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1016\/S0022-3565(25)39191-3","article-title":"3,4\u2010Methylenedioxymethamphetamine and 3,4\u2010methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine\u2010labeled serotonin uptake sites","volume":"242","author":"Battaglia G","year":"1987","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-006-0322-6"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1996.67020669.x"},{"key":"e_1_2_5_7_1","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1080\/j.1440-1614.2005.01628.x","article-title":"Acute tryptophan depletion. 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