{"id":3208,"date":"2020-06-13T18:32:16","date_gmt":"2020-06-13T16:32:16","guid":{"rendered":"http:\/\/www3.uah.es\/dianas\/journal\/dianas-2016-5-1-article-title-3068-copy-3\/"},"modified":"2020-06-13T18:32:16","modified_gmt":"2020-06-13T16:32:16","slug":"dianas-2016-5-1-e20160342-abuin-etal-a-single-neurotoxic-dose-of-mdma-increases-kynurenine-pathway-metabolism-in-plasma-and-hippocampus-of-rat","status":"publish","type":"post","link":"https:\/\/dianas.web.uah.es\/journal\/dianas-2016-5-1-e20160342-abuin-etal-a-single-neurotoxic-dose-of-mdma-increases-kynurenine-pathway-metabolism-in-plasma-and-hippocampus-of-rat\/","title":{"rendered":"dianas 5 (1) Abuin etal 2016 A single neurotoxic dose of MDMA increases kynurenine pathway metabolism in plasma and hippocampus of rat."},"content":{"rendered":"
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dianas 5(1)
<\/a> > Abuin etal
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dianas | Vol 5 Num 1 | marzo 2016 | e20160342
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Cristina Abuin, Rebeca Vidal, Mar\u00eda Dolores Guti\u00e9rrez, Esther O\u2019Shea, Mar\u00eda Isabel Colado<\/p>\n\n

Departamento de Farmacolog\u00eda, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain.
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camartinez@ucm.es
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I Congreso de Se\u00f1alizaci\u00f3n Celular, SECUAH 2016

\nDepartamento de Biolog\u00eda de Sistemas, Facultad de Medicina, Universidad de Alcal\u00e1 (UAH). Alcal\u00e1 de Henares, Madrid (Spain)
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Resumen<\/p>\n

Introduction<\/strong>: The kynurenine pathway is the main route of tryptophan metabolism and under physiological conditions, it is responsible for over 95% of tryptophan degradation in mammals. Tryptophan is converted into the first stable molecule of the pathway, kynurenine, through the action of the enzymes tryptophan 2,3-dioxygenase and indoleamine 2,3-dioxygenase. The pathway is divided into two branches, one of which forms kynurenic acid by means of kynurenine aminotransferases, and the other of which, by the action of kynurenine mono-oxygenase, gives rise to 3-hydroxykynurenine, a precursor of the neurotoxin quinolinic acid. Kynurenine, kynurenic acid and quinolinic acid have been implicated in various neurological and neurodegenerative disorders [1]. 3,4-Methylenedioxymethamphetamine (MDMA, \u2018ecstasy\u2019) is an amphetamine derivative that produces serotonergic neurotoxicity [2] and neuroinflammation manifested as increased production of interleukin-1\u03b2 and microglial activation [3]. Objective<\/strong>: The aim of this study was to evaluate possible changes in the levels of major kynurenine pathway metabolites following MDMA administration. Materials and methods: <\/strong>Male Dark Agouti rats received a single neurotoxic dose of MDMA (12.5 mg\/kg, i.p.) and were sacrificed 1 h, 3 h, 6 h, 24 h or 7 days later. Plasma and hippocampal concentrations of serotonin, tryptophan, kynurenine and kynurenic acid were measured by high pressure liquid chromatography. The ratios of serotonin\/tryptophan and kynurenine\/tryptophan were also calculated as an index of the activity of the enzymes involved in the metabolism of tryptophan. Results: <\/strong>MDMA increases hippocampal concentrations of tryptophan 1 h and 3 h after administration, returning to control concentrations at 6 h. No differences in plasma concentrations of tryptophan occur at any of the times measured compared with the control group. Kynurenine concentrations are also raised in hippocampus 1 h, 3 h and 6 h after MDMA as are the plasma concentrations 3 h and 6 h after drug administration. Furthermore, in hippocampus the kynurenine\/tryptophan ratio is increased only 6 h after MDMA whereas in plasma, an increase is observed after 1 h, 3 h and 6 h. MDMA raises kynurenic acid concentrations at 6 h in hippocampus and at 3 h in plasma. Serotonin concentrations decrease in hippocampus at all the time-points evaluated, and in plasma at 3 h and 6 h. The serotonin\/tryptophan ratio also decreases in hippocampus at all the times measured but only at 3 h and 6 h in plasma. Conclusions: <\/strong>Administration of a neurotoxic dose of MDMA in Dark Agouti rats leads to an imbalance of the kynurenine pathway, resulting in an increase in the kynurenine\/tryptophan ratio in plasma and hippocampus reflecting an increase in IDO activity.<\/p><\/p>\n\n

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