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
January 1, 2005
Isabel Escobedo, Esther O’shea, Laura Orío et al.
68 citations
MDMA itself does not cause the immediate release of dopamine or serotonin in the mouse brain; instead, peripheral injection of MDMA reduced striatal dopamine and modestly reduced serotonin one hour after the last dose, but direct injection into the striatum did not produce these acute effects. The metabolite HHMA also did not contribute to acute dopamine depletion, as its effects differed from MDMA after peripheral injection. Long-term dopamine loss seven days later was not due to MDMA itself, since only very high intrastriatal doses caused such loss, and HHMA did not alter striatal dopamine after peripheral injection. HHMA crossed the blood–brain barrier but was not detected in brain after peripheral MDMA, suggesting it is metabolized to other active compounds.
Journal of Psychopharmacology
September 1, 2004
Verónica Sánchez, Esther O’shea, Kathryn S. Saadat et al.
66 citations
Repeated doses of MDMA (ecstasy) given to rats in a single session cause a dose-dependent increase in body temperature and long-term damage to serotonin neurons in the brain, but not to dopamine neurons. A dosing schedule of three injections of 4 mg/kg led to about a 50% loss of serotonin in the hippocampus, cortex, and striatum, while three injections of 6 mg/kg led to about a 65% loss. When rats were housed in a hot environment (30 °C), the same dose produced a larger temperature increase (up to 2.6 °C) and a 65% loss of serotonin in the cortex and hippocampus, with no loss of dopamine in the striatum.
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.