Serotonergic deficits and impaired passive-avoidance learning in rats by MDEA: a comparison with MDMA.
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.
Barrionuevo
M
M
Department of Pharmacology, University of Navarra, Pamplona, Spain.
Aguirre
N
N
Del Río
J D
JD
Lasheras
B
B
D015104:3,4-Methylenedioxyamphetamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D002352:Carrier Proteins / Q000187:drug effects / Q000378:metabolism; D015198:Designer Drugs / Q000494:pharmacology*; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000187:drug effects / Q000378:metabolism; D026901:Membrane Transport Proteins; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D009419:Nerve Tissue Proteins; D017374:Paroxetine / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin / Q000378:metabolism*; D018490:Serotonin Agents / Q000494:pharmacology*; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors / Q000378:metabolism
D015104:3,4-Methylenedioxyamphetamine; D002352:Carrier Proteins; D015198:Designer Drugs; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D009419:Nerve Tissue Proteins; D017374:Paroxetine; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin; D018490:Serotonin Agents; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C493232:Slc6a4 protein, rat; C051800:3,4-methylenedioxyethamphetamine