Behavioral and neurochemical effects of orally administered MDMA in the rodent and nonhuman primate

Neurotoxicology. 1989 Fall;10(3):529-42.


MDMA (methylenedioxymethamphetamine) is a recreational drug of abuse known as "Ecstasy" which markedly decreases regional brain serotonin (5-HT) content and produces 5-HT nerve terminal degeneration in forebrain areas of the rat. In order to determine the acute and chronic behavioral effects of MDMA, adult rats were given MDMA at 0, 5 or 10 mg/kg, po for 4 consecutive days. Alternatively, parachloroamphetamine (PCA) at 5 mg/kg was administered under the same regimen. Within 30 min after the first dose, the MDMA-treated rats exhibited the serotonin motor syndrome consisting of straub tail and splayed hindlimbs comparable to that seen in the PCA-treated rats. This serotonin motor syndrome, with a duration of about 2 hr, was less pronounced after subsequent doses. At 2-4 wk after the last dose, no significant differences between control and treated rats were seen in emergence, hot plate response, auditory startle response or complex maze behavior even though a significant dose-related decrease (50%) in 5-HT concentration was observed in the frontal cortex and hippocampus of these rats 4 wks after the last dose. Adult female monkeys dosed po with 5 or 10 mg/kg of MDMA twice/day for 4 consecutive days demonstrated no spontaneous behavioral changes or weight loss compared to controls, but forebrain 5-HT concentration was reduced by 80% 1 mon after dosing. These data indicate that at doses only 2-3 times the human dose, MDMA produces significant forebrain 5-HT decreases but does not produce detectable residual behavioral alterations as assessed by these behavioral paradigms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3,4-Methylenedioxyamphetamine / analogs & derivatives
  • 3,4-Methylenedioxyamphetamine / toxicity*
  • Amphetamines / toxicity*
  • Animals
  • Behavior, Animal / drug effects*
  • Biogenic Monoamines / metabolism
  • Brain Chemistry / drug effects*
  • Conditioning, Operant / drug effects
  • Female
  • Macaca mulatta
  • Male
  • N-Methyl-3,4-methylenedioxyamphetamine
  • Radioimmunoassay
  • Rats
  • Rats, Inbred Strains
  • Reaction Time / drug effects
  • Reflex, Startle / drug effects
  • Sex Factors
  • beta-Endorphin / metabolism
  • p-Chloroamphetamine / toxicity


  • Amphetamines
  • Biogenic Monoamines
  • 3,4-Methylenedioxyamphetamine
  • beta-Endorphin
  • p-Chloroamphetamine
  • N-Methyl-3,4-methylenedioxyamphetamine