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
July 4, 2005
A Richard Green, Esther O’shea, Kathryn S. Saadat et al.
70 citations
In rats, MDMA (ecstasy) causes hyperthermia at normal or warm room temperatures but hypothermia in cool conditions. At 15°C, MDMA rapidly lowered rectal temperature; this effect was blocked by a dopamine D2 receptor antagonist but not a D1 antagonist. A neurotoxic MDMA regimen reduced serotonin in the brain by about 30% after a week. This serotonin lesion did not affect tail temperature increases when rats moved from 20°C to 30°C, but led to lower tail temperatures when returned to 24°C. Acute MDMA in lesioned rats at 30°C caused a sustained drop in tail temperature. The findings suggest that thermoregulatory problems in MDMA-lesioned rats stem partly from impaired heat loss through the tail, a key heat-loss organ.
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.
Journal of Psychopharmacology
October 10, 2012
Cheryl M Collins, Joris Kloek, J.m. Elliott
28 citations
In rats, MDMA (20 mg/kg) caused a parallel drop in serotonin levels in the frontal cortex and blood, with decreases of 63% and 46% respectively at 2 hours, partial recovery by 8 hours (42% and 38% below control), and further recovery by 18 hours (19% and 24% below control). A tryptophan supplement (82.5 mg/kg) raised serotonin in both brain (39%) and blood (26%) in naïve rats, but after MDMA, the same supplement raised brain serotonin only 26% and had no effect on blood serotonin. Blood serotonin appears to be a useful marker for brain serotonin levels after acute MDMA, suggesting platelet serotonin could serve similarly in human studies.
British Journal of Clinical Pharmacology
April 1, 1985
Michael Schächter, D.p. Geaney, Dg Grahame‐smith et al.
20 citations
Schizophrenic patients treated with depot thioxanthenes and phenothiazines showed an approximately 30% increase in platelet 5-HT receptor number and a roughly 30% decrease in receptor affinity compared to controls. The decrease in affinity likely resulted from residual neuroleptic in the platelet membrane preparation. A weak positive correlation existed between receptor number and total neuroleptic dosage. The increased receptor number aligns with earlier reports of enhanced 5-HT-induced platelet aggregation in patients on long-term phenothiazines and thioxanthenes, suggesting 5-HT up-regulation in human platelets from depot neuroleptic therapy. Whether parallel changes occur in brain 5-HT receptors remains unknown.
Cellular and Molecular Life Sciences
February 1, 1988
A. David Smith, D.p. Geaney, Michael Schächter et al.
15 citations
Chronic treatment with phenothiazines and thioxanthenes enhances serotonin-induced aggregation of human platelets. Using radiolabeled LSD, researchers found that the LSD binding site on platelets is the same as the 5-HT2 receptor responsible for shape change and aggregation. In patients receiving these neuroleptics, the number of binding sites (Bmax) increased, while binding affinity decreased, possibly due to residual drug in the membrane. The increased binding capacity was not explained by this persistence. Chronic treatment 'up-regulates' platelet 5-HT2 binding sites, which may increase sensitivity to serotonin-induced aggregation. In normal subjects, desipramine treatment also increased binding site number, accompanied by a greater prolactin response to tryptophan, suggesting a link to central serotonin function.