• Media type: E-Article
  • Title: In vitro neuronal and vascular responses to 5‐HT in rats chronically exposed to MDMA
  • Contributor: Cannon, Dara M; Keenan, Alan K; Guiry, Patrick J; Buon, Christophe; Baird, Alan W; McBean, Gethin J
  • imprint: Wiley, 2001
  • Published in: British Journal of Pharmacology
  • Language: English
  • DOI: 10.1038/sj.bjp.0704402
  • ISSN: 1476-5381; 0007-1188
  • Keywords: Pharmacology
  • Origination:
  • Footnote:
  • Description: <jats:p> <jats:list list-type="explicit-label"> <jats:list-item><jats:p>This study examined the effects of chronic exposure of rats to 3,4‐methylenedioxymethamphetamine (MDMA) on [<jats:sup>3</jats:sup>H]5‐hydroxytryptamine ([<jats:sup>3</jats:sup>H]5‐HT) re‐uptake into purified rat brain synaptosomes, 5‐HT‐induced isometric contraction of aortic rings and [<jats:sup>3</jats:sup>H]5‐HT re‐uptake into rat aorta.</jats:p></jats:list-item> <jats:list-item><jats:p>Rats were administered MDMA (20 mg kg<jats:sup>−1</jats:sup> i.p.) twice daily over 4 days. One, 7, 14 or 21 days post treatment, whole brain synaptosomes and descending thoracic aortic rings were prepared for investigation.</jats:p></jats:list-item> <jats:list-item><jats:p>Chronic MDMA treatment significantly reduced the maximum rate (V<jats:sub>max</jats:sub>) of specific high‐affinity [<jats:sup>3</jats:sup>H]5‐HT re‐uptake 1 day after treatment and for up to 21 days post‐final administration of MDMA. Direct application of MDMA (100 μ<jats:sc>M</jats:sc>) abolished synaptosomal re‐uptake of [<jats:sup>3</jats:sup>H]5‐HT <jats:italic>in vitro</jats:italic>.</jats:p></jats:list-item> <jats:list-item><jats:p>Chronic MDMA administration significantly reduced the maximum contraction (E<jats:sub>max</jats:sub>) to 5‐HT at 1 and 7 days after treatment, but not at 14 or 21 days.</jats:p></jats:list-item> <jats:list-item><jats:p>Chronic MDMA administration had no effect on sodium‐dependent [<jats:sup>3</jats:sup>H]5‐HT re‐uptake into aorta 1 day after treatment, nor did 100 μ<jats:sc>M</jats:sc> MDMA have any direct effect on [<jats:sup>3</jats:sup>H]5‐HT uptake into aortic rings <jats:italic>in vitro</jats:italic>.</jats:p></jats:list-item> <jats:list-item><jats:p>These results show, for the first time, an altered responsiveness of vascular tissue to MDMA after chronic administration. In addition, they demonstrate a difference in the sensitivity of central and peripheral 5‐HT uptake systems to chronic MDMA exposure, and suggest that the action of MDMA in the cardiovascular system does not arise from a direct effect of MDMA on peripheral 5‐HT transport.</jats:p></jats:list-item> </jats:list> </jats:p><jats:p><jats:italic>British Journal of Pharmacology</jats:italic> (2001) <jats:bold>134</jats:bold>, 1455–1460; doi:<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" xlink:href="10.1038/sj.bjp.0704402">10.1038/sj.bjp.0704402</jats:ext-link></jats:p>
  • Access State: Open Access