British Journal of Pharmacology
June 1, 1997
M. Isabel Colado, Esther O’shea, R Granados et al.
176 citations
High doses of MDMA (ecstasy) given to pregnant rats on days 14–17 of gestation caused a marked hyperthermic response in the mothers, reduced their body weight, and decreased litter size by about 20%. In the mothers' brains, serotonin (5-HT) and its metabolite 5-HIAA fell by over 65% in the hippocampus and striatum and by 40% in the cortex one week after birth. However, the brains of the newborn pups showed no such decreases. MDMA also increased lipid peroxidation (TBARS) in the cortex of adult rats but not in 7–10 day old neonates.
British Journal of Pharmacology
July 1, 1997
María Isabel Colado, Esther O’shea, R Granados et al.
175 citations
MDMA (ecstasy) and p-chloroamphetamine (PCA) damage serotonin neurons in rat brain by increasing free radical formation, measured as 2,3-dihydroxybenzoic acid from salicylic acid via microdialysis in the hippocampus. A single dose of MDMA (15 mg/kg) raised 2,3-DHBA for at least 6 hours and reduced serotonin and its metabolite by over 50% in hippocampus, cortex, and striatum seven days later. PCA (5 mg/kg) also increased 2,3-DHBA. Fenfluramine (15 mg/kg) did not increase free radicals but still caused long-term serotonin loss. Pretreatment with fenfluramine blocked MDMA's free radical rise, indicating radicals originate in serotonin neurons. The free radical scavenger PBN prevented the acute radical increase and attenuated long-term hippocampal damage by 30%. Thus, MDMA and PCA damage serotonin neurons via free radicals, while fenfluramine acts through a different mechanism.
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.