Received for publication April 25, 2005.
Revised June 1, 2005.
Accepted for publication June 1, 2005.

(±)-3,4-Methylenedioxymethamphetamine (MDMA) Administration to Rats Does Not Decrease Levels of the Serotonin Transporter Protein or Alter its Distribution Between Endosomes and the Plasma Membrane

Abstract

We showed that the 5-HT neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT), reduces brain tissue 5-HT, decreases expression of 5-HT transporter (SERT) protein and increases expression of glial fibrillary acidic protein (GFAP). In contrast, doses of (±)-3,4-methylenedioxymethamphetamine (MDMA) that decrease brain tissue 5-HT fail to alter expression of SERT or GFAP. Using a new and highly sensitive anti-SERT antibody, we determined if MDMA alters the subcellular distribution of SERT protein by measuring SERT expression in endosomes and plasma membranes 2 weeks after MDMA administration. Rat brain tissues (caudate, cortex, hippocampus) were collected 3 days and 2 weeks after MDMA (7.5 mg/kg i.p., q 2hr x 3 doses) or 5,7-DHT (150 µg/rat, icv) administration. Representative results from cortex are as follows. At both 3 days and 2 weeks post-injection, MDMA decreased tissue 5-HT (60%) and had no effect on GFAP expression. MDMA increased HSP32 (a marker for microglial activation) expression (25%) at 3 days, but not 2 weeks. MDMA did not alter SERT expression at either time point and did not alter SERT levels in either endosomes or plasma membranes (2 weeks). 5,7-DHT decreased tissue 5-HT (80%), increased HSP32 expression at both time points (about 50%), and increased GFAP expression at 2 weeks (37%). 5,7-DHT decreased SERT expression (33%) at 2-weeks but not at 3-days. These findings indicate that a dosing regimen of MDMA that depletes brain 5-HT does not alter SERT protein expression or the distribution of SERT between endosomes and the plasma membrane, and does not produce detectable evidence for neurotoxicity.

Key words: MDMA, endosome, methamphetamine, methylenedioxymethamphetamine, microglia, serotonin transporter

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