{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:08:33Z","timestamp":1760216913259},"reference-count":33,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2004,7,14]],"date-time":"2004-07-14T00:00:00Z","timestamp":1089763200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Synapse"],"published-print":{"date-parts":[[2004,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Previous experiments conducted in this laboratory showed that administration of high\u2010dose D\u2010fenfluramine (D\u2010FEN) and p\u2010chloroamphetamine (PCA) decreased 5\u2010HT transporter (SERT) binding and tissue 5\u2010HT by 30\u201360% in caudate and whole brain tissue 2 days and 2 weeks after drug administration. However, protein expression as determined by Western blot analysis did not change in either tissue or time point, except for a 30% decrease in the caudate 2 days after PCA administration. In the present study, we studied the effect of MDMA and 5,7\u2010dihydroxytryptamine (5,7\u2010DHT) on tissue 5\u2010HT levels and the protein expression level of SERT and glial fibrillary acidic protein (GFAP), a validated neurotoxicity marker. <jats:styled-content>Hypothesis.<\/jats:styled-content> MDMA administration decreases SERT expression. <jats:styled-content>Methods.<\/jats:styled-content> Two weeks after MDMA administration (7.5 mg\/kg i.p., q 2 h \u00d7 3 doses) or 2 weeks after i.c.v. administration of 5,7,\u2010DHT (150 \u03bcg\/rat), male Sprague\u2010Dawley rats were sacrificed and the caudate, cortex, and hippocampal tissue collected. Western blots for SERT and GFAP were generated using published methods. Tissue 5\u2010HT levels were determined by HPLC coupled to electrochemical detection. <jats:styled-content>Results.<\/jats:styled-content> MDMA treatment decreased tissue 5\u2010HT in cortex, hippocampus, and caudate by about 50%. However, MDMA treatment had no significant effect on expression level of SERT and GFAP in any brain region. In contrast, 5,7\u2010DHT reduced tissue 5\u2010HT by more than 90%, decreased SERT protein expression by 20\u201335%, and increased GFAP by 30\u201339%. <jats:styled-content>Conclusion.<\/jats:styled-content> These data suggest the MDMA treatment regimen used here does not cause degeneration of 5\u2010HT nerve terminals. Viewed collectively with our previous results and other published data, these data indicate that MDMA\u2010induced persistent 5\u2010HT depletion may occur in the absence of axotomy. Synapse 53:240\u2013248, 2004. 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