Serotonergic deficits and impaired passive-avoidance learning in rats by MDEA: a comparison with MDMA

Pharmacol Biochem Behav. 2000 Feb;65(2):233-40. doi: 10.1016/s0091-3057(99)00170-7.


The serotonergic deficits induced by 3,4-methylenedioxyethamphetamine (MDEA, "eve"), were examined and compared with 3,4 methylenedioxymethamphetamine (MDMA, "ecstasy"). A single dose of MDEA (10, 20, or 40 mg/kg IP) induced a dose-related hyperthermia, but only the highest dose significantly reduced 5-HT content and 5-HT transporter density in the frontal cortex and in the hippocampus 7 days later. Long-term serotonergic deficits were much more marked when MDEA was given repeatedly (40 mg/kg IP., b.i.d., for 4 consecutive days). Single or repeated administration of MDEA induced no change on 5-HT1A receptor density in the frontal cortex, brain stem, or hippocampus, although 3 h after both treatments plasma corticosterone levels were significantly increased. MDEA (5-20 mg/kg, IP) produced significant retention deficits in a passive-avoidance learning task. Conversely, 7 days after the repeated administration of MDEA (40 mg/kg b.i.d., for 4 consecutive days) no effect on passive-avoidance performance was observed unless rats were treated again with another dose of MDEA (20 mg/kg IP) 30 min before the training trial. The 5-HT1A receptor antagonist, WAY 100635, prevented the impairment in retention performance induced by 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), but not by MDEA or MDMA, indicating that the effect of these amphetamine derivates was not mediated by 5-HT1A receptor activation. The results suggest the risk of serotonergic dysfunction associated with MDEA abuse in humans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3,4-Methylenedioxyamphetamine / analogs & derivatives*
  • 3,4-Methylenedioxyamphetamine / pharmacology
  • Animals
  • Avoidance Learning / drug effects*
  • Carrier Proteins / drug effects
  • Carrier Proteins / metabolism
  • Designer Drugs / pharmacology*
  • Frontal Lobe / drug effects
  • Frontal Lobe / metabolism
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Male
  • Membrane Glycoproteins / drug effects
  • Membrane Glycoproteins / metabolism
  • Membrane Transport Proteins*
  • N-Methyl-3,4-methylenedioxyamphetamine / pharmacology*
  • Nerve Tissue Proteins*
  • Paroxetine / metabolism
  • Rats
  • Rats, Wistar
  • Receptors, Serotonin / drug effects*
  • Receptors, Serotonin / metabolism
  • Receptors, Serotonin, 5-HT1
  • Selective Serotonin Reuptake Inhibitors / metabolism
  • Serotonin / metabolism*
  • Serotonin Agents / pharmacology*
  • Serotonin Plasma Membrane Transport Proteins


  • Carrier Proteins
  • Designer Drugs
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT1
  • Serotonin Agents
  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin Uptake Inhibitors
  • Slc6a4 protein, rat
  • Serotonin
  • Paroxetine
  • 3,4-Methylenedioxyamphetamine
  • N-Methyl-3,4-methylenedioxyamphetamine
  • 3,4-methylenedioxyethamphetamine