The effects of 3 successive ascending doses of MDMA (10, 15 and 20 mg/kg) on circadian rhythm in the Syrian hamster were investigated by measuring degree of circadian rhythm alteration produced by the 5HT1A/5HT7 agonist 8-hydroxy-2-di-n-propylamine-tetralin (8-OHDPAT). After a 14 light: 10 dark (LD) cycle, hamsters were kept for 7 days in constant darkness, and then exposed to a 15 min light pulse (referred to as "Aschoff 1"), and wheel running activity was monitored for 10 days, followed by 5 mg/kg 8-OHDPAT. Either vehicle or MDMA was then administered, and the same procedure (constant darkness, 15 min light pulse and 8-OHDPAT administration 10 days later) repeated. In another study, Syrian hamsters experienced a 14:10 LD schedule instead of constant darkness ("Aschoff 2"), received a light pulse and 8-OHDPAT before lights off, with both stimuli usually producing a phase advance in circadian rhythm. MDMA administration reduced 8-OHDPAT-induced phase advance in the Aschoff 1 study. Hamsters also demonstrated a smaller phase shift after the light pulse after MDMA administration than vehicle-treated animals. Similar reduction in phase advance in MDMA-treated hamsters was found in the Aschoff 2 paradigm, both in response to 8-OHDPAT and light pulse before lights-off. The authors did not report any histological studies of serotonin-containing areas of brain in these studies, but nevertheless hypothesize that MDMA-induced harm to serotonin axons connecting to the suprachiasmatic nucleus (SCN), medial, or dorsal raphe attenuated phase advance after light or 8-OHDPAT. The authors note that the serotonergic neurotoxin 5,7-DHT potentiates phase shifts to light in mice and hamsters, and hypothesize that MDMA and 5,7-DHT produce different effects because the two compounds have mechanisms of neurotoxicity, with 5,7-DHT destroying cell bodies and MDMA destroying axons. At least one other published report of changes in circadian rhythm in rodents given MDMA exists (Wallace et al. 2001). Phase advances in circadian rhythm either after acute or regular MDMA/ecstasy use have never been investigated in humans. Furthermore, findings of changes in sleep in regular ecstasy users remains inconclusive, and concern changes in sleep architecture (Allen et al. 1993) rather than changes in circadian rhythm. Beyond indicating a sign of long-term effects of MDMA in rodents, this study is not clearly relevant to humans.