RATIONALE: There is some uncertainty whether the acute hyperthermia caused by MDMA (ecstasy) plays a significant role in determining the long-term neurotoxic effects on brain 5-HT systems and associated changes in mood and behaviour. OBJECTIVE: The present study assessed whether long-term behavioural and cognitive changes seen in MDMA-treated rats are affected by hyperthermia at the time of drug administration. METHOD: Male Wistar rats were treated with MDMA (4x5 mg/kg i.p. over 4 h on 2 consecutive days) or vehicle at either a high ambient temperature (28 degrees C) or a low ambient temperature (16 degrees C). Eight to 18 weeks later, rats were tested in behavioural measures of anxiety (social interaction and emergence tests), a test of cognition (object recognition test) and the forced swim test of depression. At the conclusion of behavioural testing the rats were killed and their brains analysed using HPLC. RESULTS: MDMA treatment caused a clear and consistent hyperthermia at 28 degrees C and hypothermia at 16 degrees C. Months later, rats pre-treated with MDMA at either 16 or 28 degrees C displayed increased anxiety in the social interaction and emergence tests and reduced escape attempts and increased immobility in the forced swim test. MDMA pre-treatment was also associated with poorer memory on the object recognition test, but only in rats given the drug at 28 degrees C. Rats pre-treated with MDMA showed loss of 5-HT in the hippocampus, striatum, amygdala and cortex, regardless of body temperature at the time of dosing. However, 5-HIAA loss in the amygdala and hippocampus was greater in rats pre-treated at 28 degrees C. Dopamine in the striatum was also depleted in rats given MDMA. CONCLUSIONS: These results indicate that hyperthermia at the time of dosing with MDMA is not necessary to produce subsequent 5-HT depletion and anxiety in rats. They also extend previous findings of long-term effects of brief exposure to MDMA in rats to include apparent "depressive" symptoms in the forced swim model.
RATIONALE: There is some uncertainty whether the acute hyperthermia caused by MDMA (ecstasy) plays a significant role in determining the long-term neurotoxic effects on brain 5-HT systems and associated changes in mood and behaviour. OBJECTIVE: The present study assessed whether long-term behavioural and cognitive changes seen in MDMA-treated rats are affected by hyperthermia at the time of drug administration. METHOD: Male Wistar rats were treated with MDMA (4x5 mg/kg i.p. over 4 h on 2 consecutive days) or vehicle at either a high ambient temperature (28 degrees C) or a low ambient temperature (16 degrees C). Eight to 18 weeks later, rats were tested in behavioural measures of anxiety (social interaction and emergence tests), a test of cognition (object recognition test) and the forced swim test of depression. At the conclusion of behavioural testing the rats were killed and their brains analysed using HPLC. RESULTS:MDMA treatment caused a clear and consistent hyperthermia at 28 degrees C and hypothermia at 16 degrees C. Months later, rats pre-treated with MDMA at either 16 or 28 degrees C displayed increased anxiety in the social interaction and emergence tests and reduced escape attempts and increased immobility in the forced swim test. MDMA pre-treatment was also associated with poorer memory on the object recognition test, but only in rats given the drug at 28 degrees C. Rats pre-treated with MDMA showed loss of 5-HT in the hippocampus, striatum, amygdala and cortex, regardless of body temperature at the time of dosing. However, 5-HIAA loss in the amygdala and hippocampus was greater in rats pre-treated at 28 degrees C. Dopamine in the striatum was also depleted in rats given MDMA. CONCLUSIONS: These results indicate that hyperthermia at the time of dosing with MDMA is not necessary to produce subsequent 5-HT depletion and anxiety in rats. They also extend previous findings of long-term effects of brief exposure to MDMA in rats to include apparent "depressive" symptoms in the forced swim model.
Authors: Ann M Hemmerle; Jonathan W Dickerson; Nicole R Herring; Tori L Schaefer; Charles V Vorhees; Michael T Williams; Kim B Seroogy Journal: J Comp Neurol Date: 2012-08-01 Impact factor: 3.215
Authors: Ratchanee Rodsiri; Clare Spicer; A Richard Green; Charles A Marsden; Kevin C F Fone Journal: Psychopharmacology (Berl) Date: 2010-07-20 Impact factor: 4.530
Authors: Matthew R Skelton; Jessica A Able; Curtis E Grace; Nicole R Herring; Tori L Schaefer; Gary A Gudelsky; Charles V Vorhees; Michael T Williams Journal: Neuropharmacology Date: 2008-07-12 Impact factor: 5.250
Authors: Petra S van Nieuwenhuijzen; Leonora E Long; Glenn E Hunt; Jonathon C Arnold; Iain S McGregor Journal: Psychopharmacology (Berl) Date: 2010-08-21 Impact factor: 4.530
Authors: Dominik K Biezonski; Brian J Piper; Nina M Shinday; Peter J Kim; Syed F Ali; Jerrold S Meyer Journal: Eur J Pharmacol Date: 2012-12-28 Impact factor: 4.432
Authors: Cynthia A Crawford; Michael T Williams; Jodie L Kohutek; Fiona Y Choi; Shelly T Yoshida; Sanders A McDougall; Charles V Vorhees Journal: Brain Res Date: 2006-02-14 Impact factor: 3.252