Memory deficit and reduced anxiety in young adult rats given repeated intermittent MDMA treatment during the periadolescent period

Pharmacol Biochem Behav. 2004 Dec;79(4):723-31. doi: 10.1016/j.pbb.2004.10.001.


3,4-Methylenedioxymethamphetamine (MDMA, or "Ecstasy") is a popular recreational drug among adolescents that is often taken primarily on weekends. The goals of this study were to develop a model of the typical intermittent pattern of human MDMA use in periadolescent rats and to determine the behavioral consequences of MDMA exposure in this model. Male Sprague-Dawley rats received s.c. injections of 10 mg/kg of MDMA or saline twice daily with an interdose interval of 4 h. Treatments were given every fifth day from postnatal day (PD) 35 to PD 60. Beginning at PD 65, the animals were tested for open-field activity, object recognition memory, and anxiety-related behaviors in the elevated plus-maze. Brain tissues were collected at PD 70 for determination of radiolabeled paroxetine binding to the serotonin transporter (SERT) in the neocortex and hippocampus. Repeated MDMA administration led to a reduced rate of weight gain that was evident by PD 50. There was no treatment effect on ambulatory behavior in the open-field. However, the MDMA group displayed an impairment of object recognition memory and reduced anxiety as indicated by a twofold increase in open-arm duration in the elevated plus-maze. Only modest decreases in SERT binding were observed, although there was a significant negative correlation between hippocampal SERT levels and open-arm duration within the MDMA group. These findings demonstrate that intermittent MDMA exposure during the adolescent period of development can influence subsequent cognitive and affective functioning in the absence of severe serotonergic damage.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Age Factors
  • Animals
  • Anxiety / drug therapy*
  • Anxiety / metabolism
  • Anxiety / psychology
  • Male
  • Membrane Glycoproteins / metabolism
  • Membrane Transport Proteins / metabolism
  • Memory Disorders / chemically induced*
  • Memory Disorders / metabolism
  • Memory Disorders / psychology
  • N-Methyl-3,4-methylenedioxyamphetamine / administration & dosage*
  • N-Methyl-3,4-methylenedioxyamphetamine / metabolism
  • Nerve Tissue Proteins / metabolism
  • Protein Binding / drug effects
  • Protein Binding / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Serotonin Plasma Membrane Transport Proteins


  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • Serotonin Plasma Membrane Transport Proteins
  • Slc6a4 protein, rat
  • N-Methyl-3,4-methylenedioxyamphetamine