British Journal of Pharmacology
December 1, 2001
M. Isabel Colado, Jorge Camarero, Annis O. Mechan et al.
122 citations
MDMA (ecstasy) causes long-term damage to dopamine nerve terminals in the mouse striatum, accompanied by acute hyperthermia. Blocking NMDA receptors or using clomethiazole did not protect against this damage. The free radical trap PBN and the nitric oxide synthase inhibitor 7-NI were protective but also lowered body temperature. Two other NOS inhibitors, S-methyl-L-thiocitrulline and AR-R17477AR, provided significant neuroprotection with little effect on hyperthermia. MDMA increased free radical formation in the striatum, which was prevented by AR-R17477AR, which lacks radical-trapping activity. This suggests MDMA neurotoxicity involves radicals from MDMA or dopamine metabolites combining with nitric oxide to form damaging peroxynitrites.
British Journal of Pharmacology
September 1, 2001
Violeta Sánchez Sánchez, Jorge Camarero, B. Moreno Esteban et al.
103 citations
Fluoxetine provides long-lasting protection against MDMA-induced damage to serotonin nerve endings in rat brain, while fluvoxamine only protects when given at the same time. MDMA caused loss of serotonin and its metabolite in cortex, hippocampus, and striatum, and reduced paroxetine binding one week later. Fluoxetine given with MDMA or up to four days before offered complete protection, and significant protection when given seven days before. Fluvoxamine required concurrent administration. Fluoxetine's protection appears due to its and its active metabolite's inhibition of the serotonin transporter, not by altering MDMA accumulation or metabolism.
British Journal of Pharmacology
June 12, 2006
Esther O’shea, Laura Orío, Isabel Escobedo et al.
57 citations
MDMA (ecstasy) causes long-term damage to serotonin neurons in the rat brain, but measuring serotonin levels alone may overestimate the extent of that damage. In male DA rats given a single dose of MDMA, serotonin content and a marker of serotonin nerve terminals were reduced in the cortex and hippocampus for up to 32 weeks. The activity of the enzyme that makes serotonin was also reduced for 8 weeks but recovered by 32 weeks. Housing rats in a cold environment prevented the loss of nerve-terminal markers but not the drop in serotonin levels, suggesting that the serotonin loss partly reflects enzyme inhibition rather than only neuron death. The damaged neurons did not increase serotonin production to compensate.