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
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
July 1, 1981
A R Green, J E Hall, A R Rees
88 citations
Several drugs that block serotonin (5-HT) receptors were tested for their effects on behaviors in rats induced by increasing serotonin activity. Methysergide, methergoline, methiothepin, and (-)-propranolol inhibited head weaving, forepaw treading, and hind-limb abduction, while cyproheptadine, cinanserin, and mianserin had no effect. At a higher dose, cyproheptadine did inhibit the behaviors. Methiothepin also blocked dopamine-related activity, suggesting its effects involve dopamine antagonism. Depleting serotonin with p-chlorophenylalanine enhanced responses to serotonin agonists. The findings suggest that some drugs fail to block serotonin-induced behaviors because they are weak antagonists, and caution is needed when interpreting serotonin's role in behaviors based on single antagonists.
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.