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 com pared with 3,4 methylenedioxymethamphetamin e (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 reduc ed 5-HT content and 5-HT transporter density in the frontal cortex and in t he 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 consecu tive 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 signif icantly increased. MDEA (5-20 mg/kg, IP) produced significant retention def icits in a passive-avoidance learning task. Conversely, 7 days after the re peated administration of MDEA (40 mg/kg b.i.d., for 4 consecutive days) no effect on passive-avoidance performance was observed unless rats were treat ed 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 impairmen t in retention performance induced by 8-hydroxy-2-(di-n-propylamino) tetral in (8-OH-DPAT), but not by MDEA or MDMA, indicating that the effect of thes e amphetamine derivates was not mediated by 5-HT1A receptor activation. The results suggest the risk of serotonergic dysfunction associated with MDEA abuse in humans. (C) 2000 Elsevier Science Inc.