Increased anxiety and "depressive" symptoms months after MDMA ("ecstasy") in rats: drug-induced hyperthermia does not predict long-term outcomes

Iain S. McGregor*, Clint G. Gurtman, Kirsten C. Morley, Kelly J. Clemens, Arjan Blokland, Kong M. Li, Jennifer L. Cornish, Glenn E. Hunt

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

77 Citations (Scopus)


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°C) or a low ambient temperature (16°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°C and hypothermia at 16°C. Months later, rats pre-treated with MDMA at either 16 or 28°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°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°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.

Original languageEnglish
Pages (from-to)465-474
Number of pages10
Issue number4
Publication statusPublished - Aug 2003
Externally publishedYes


  • 5-HT
  • Anxiety
  • Depression
  • Ecstasy
  • MDMA
  • Serotonin
  • Temperature


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