التفاصيل البيبلوغرافية
| العنوان: |
MDMA-induced neurotoxicity: long-term effects on 5-HT biosynthesis and the influence of ambient temperature. |
| المؤلفون: |
O'Shea, Esther, Orio, Laura, Escobedo, Isabel, Sanchez, Veronica, Camarero, Jorge, Green, Alfred Richard, Colado, Maria Isabel |
| المصدر: |
British Journal of Pharmacology; Jul2006, Vol. 148 Issue 6, p778-785, 8p, 2 Charts, 4 Graphs |
| مصطلحات موضوعية: |
NEUROTOXICOLOGY, TOXICOLOGY, ECSTASY (Drug), HALLUCINOGENIC drugs, METHAMPHETAMINE, TRYPTOPHAN, AMINO acids |
| مستخلص: |
3,4-Methylenedioxymethamphetamine (MDMA or ‘ecstasy’) decreases the 5-HT concentration, [3H]-paroxetine binding and tryptophan hydroxylase activity in rat forebrain, which has been interpreted as indicating 5-HT neurodegeneration. This has been questioned, particularly the 5-HT loss, as MDMA can also inhibit tryptophan hydroxylase. We have now evaluated the validity of these parameters as a reflection of neurotoxicity.Male DA rats were administered MDMA (12.5 mg kg−1, i.p.) and killed up to 32 weeks later. 5-HT content and [3H]-paroxetine binding were measured in the cortex, hippocampus and striatum. Parallel groups of treated animals were administered NSD-1015 for determination of in vivo tryptophan hydroxylase activity and 5-HT turnover rate constant.Tissue 5-HT content and [3H]-paroxetine binding were reduced in the cortex (26–53%) and hippocampus (25–74%) at all time points (1, 2, 4, 8 and 32 weeks). Hydroxylase activity was similarly reduced up to 8 weeks, but had recovered at 32 weeks. The striatal 5-HT concentration and [3H]-paroxetine binding recovered by week 4 and hydroxylase activity after week 1. In all regions, the reduction in 5-HT concentration did not result in an altered 5-HT synthesis rate constant.Administering MDMA to animals when housed at 4°C prevented the reduction in [3H]-paroxetine binding and hydroxylase activity observed in rats housed at 22°C, but not the reduction in 5-HT concentration.These data indicate that MDMA produces long-term damage to serotoninergic neurones, but this does not produce a compensatory increase in 5-HT synthesis in remaining terminals. It also highlights the fact that measurement of tissue 5-HT concentration may overestimate neurotoxic damage.British Journal of Pharmacology (2006) 148, 778–785. doi:10.1038/sj.bjp.0706783; published online 12 June 2006 [ABSTRACT FROM AUTHOR] |
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