Repeated intermittent methylenedioxymethamphetamine exposure protects against the behavioral and neurotoxic, but not hyperthermic, effects of an MDMA binge in adult rats

Synapse. 2010 Jun;64(6):421-31. doi: 10.1002/syn.20744.


We have recently shown that chronic intermittent exposure of adolescent rats to 3,4-methylenedioxymethamphetamine (MDMA or Ecstasy) completely blocks the reduction in serotonin transporter (SERT) binding and the hypoactivity seen following a subsequent MDMA binge treatment. The present study determined whether a similar neuroprotective effect also occurs in rats given the same intermittent MDMA exposure in adulthood. Adult male Sprague-Dawley rats were given either MDMA (10 mg/kg x 2) or saline, every fifth day, from postnatal day (PD) 60 to PD 85. The MDMA-induced latency until seminal plug production was reduced over the course of intermittent treatments. After a 1-week wash-out period, animals received either a low- or high-dose MDMA binge (2.5 or 5.0 mg/kg x 4). Core body temperature was measured during and after the binge to determine the effects of MDMA pretreatment on MDMA-induced hyperthermia. Spontaneous motor activity was determined the next day, and cortical and hippocampal samples were collected at 1 week postbinge to measure serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) concentrations as well as [3H]citalopram binding to SERT. Hyperthermia occurred more rapidly and seminal discharge was more common in the MDMA-pretreated group compared to the MDMA-naïve group in animals given the low-dose binge. MDMA preexposure protected animals from the reductions in cortical 5-HT levels and SERT binding produced by the high-dose binge and blocked the postbinge hypoactivity. These findings indicate that chronic, intermittent MDMA exposure in adulthood induces neuroprotective effects similar to those seen with adolescent treatment. However, there was also evidence for drug-induced sensitization in adults that was not observed in adolescents. Thus, altered drug sensitivity in chronic Ecstasy users may depend not only on the frequency and pattern of use but also on the age of the user.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Binding, Competitive / drug effects
  • Binding, Competitive / physiology
  • Body Temperature / drug effects
  • Body Temperature / physiology
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Citalopram / metabolism
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Fever / chemically induced*
  • Fever / physiopathology
  • Fever / prevention & control
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Hydroxyindoleacetic Acid / metabolism
  • Male
  • Motor Activity / drug effects
  • Motor Activity / physiology
  • N-Methyl-3,4-methylenedioxyamphetamine / administration & dosage*
  • N-Methyl-3,4-methylenedioxyamphetamine / metabolism
  • N-Methyl-3,4-methylenedioxyamphetamine / toxicity*
  • Neurotoxins / metabolism
  • Neurotoxins / toxicity
  • Rats
  • Rats, Sprague-Dawley
  • Selective Serotonin Reuptake Inhibitors / metabolism
  • Serotonin / metabolism
  • Serotonin Agents / administration & dosage*
  • Serotonin Agents / metabolism
  • Serotonin Agents / toxicity*
  • Serotonin Plasma Membrane Transport Proteins / drug effects
  • Serotonin Plasma Membrane Transport Proteins / metabolism


  • Neurotoxins
  • Serotonin Agents
  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin Uptake Inhibitors
  • Citalopram
  • Serotonin
  • Hydroxyindoleacetic Acid
  • N-Methyl-3,4-methylenedioxyamphetamine