British Journal of Pharmacology
January 1, 2002
Annis O. Mechan, B. Moreno Esteban, Esther O’shea et al.
219 citations
MDMA (ecstasy) causes acute hyperthermia in rats by increasing dopamine release, which acts on D1 receptors, rather than through serotonin release. Blocking serotonin receptors or inhibiting serotonin reuptake did not prevent the rise in body temperature, but blocking D1 dopamine receptors with SCH 23390 did. The tail skin temperature did not increase, suggesting MDMA impairs heat dissipation. These findings indicate that dopamine, not serotonin, is the primary driver of MDMA-induced hyperthermia, which has implications for clinical treatment.
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
February 1, 1999
María Isabel Colado, Esther O’shea, R Granados et al.
82 citations
Dopamine does not appear to cause the damage to serotonin nerve endings that occurs in the brain of Dark Agouti rats after MDMA (ecstasy) administration. The drug haloperidol prevented both the acute rise in body temperature and the long-term loss of serotonin when given around the time of MDMA, but this protection was minimal when body temperature was kept high. MDMA increased dopamine levels in the brain by 800%, but boosting dopamine further with L-DOPA did not worsen the nerve damage, nor did it make a low, non-toxic dose of MDMA become toxic. The findings suggest that earlier studies linking dopamine to MDMA's neurotoxicity may have been confounded by effects on body temperature.
British Journal of Pharmacology
June 1, 1998
María Isabel Colado, R Granados, Esther O’shea et al.
80 citations
In rats, the drug MDMA ('ecstasy') caused a rapid rise in body temperature (hyperthermia) and, seven days later, damage to serotonin nerve endings in the brain. A low-affinity NMDA receptor blocker, AR-R15896AR, did not prevent the hyperthermia or the long-term loss of serotonin markers in the cortex, striatum, and hippocampus. In contrast, the neuroprotective agent clomethiazole abolished the hyperthermic response and markedly reduced serotonin loss—by about 75% at normal room temperature.
Pharmacology & Toxicology
June 1, 1999
María Isabel Colado, Raquel Ena María Granados, Esther O’shea et al.
26 citations
A single dose of the recreational drug MDEA ("eve") given to Dark Agouti rats caused an acute, dose-dependent rise in body temperature. The peak hyperthermia from 35 mg/kg of MDEA matched that from 15 mg/kg of MDMA ("ecstasy"). Seven days later, MDMA caused a 50% loss of serotonin and its metabolite in the cortex, hippocampus, and striatum, indicating neurotoxic damage to serotonin nerve endings. MDEA at the highest dose produced only a 20% loss in cortex and hippocampus and no loss in striatum, with weak dose dependence. Neither drug altered striatal dopamine. MDEA had about half the potency of MDMA for hyperthermia and one-quarter the potency for serotonin neuron degeneration.