3,4-methylenedioxymethamphetamine (MDMA) administration to rats decreases brain tissue serotonin but not serotonin transporter protein and glial fibrillary acidic protein.
Previous experiments conducted in this laboratory showed that administration of high-dose D-fenfluramine (D-FEN) and p-chloroamphetamine (PCA) decreased 5-HT transporter (SERT) binding and tissue 5-HT by 30-60% in caudate and whole brain tissue 2 days and 2 weeks after drug administration. However, protein expression as determined by Western blot analysis did not change in either tissue or time point, except for a 30% decrease in the caudate 2 days after PCA administration. In the present study, we studied the effect of MDMA and 5,7-dihydroxytryptamine (5,7-DHT) on tissue 5-HT levels and the protein expression level of SERT and glial fibrillary acidic protein (GFAP), a validated neurotoxicity marker.


OBJECTIVE
MDMA administration decreases SERT expression.


METHODS
Two weeks after MDMA administration (7.5 mg/kg i.p., q 2 h x 3 doses) or 2 weeks after i.c.v. administration of 5,7,-DHT (150 microg/rat), male Sprague-Dawley rats were sacrificed and the caudate, cortex, and hippocampal tissue collected. Western blots for SERT and GFAP were generated using published methods. Tissue 5-HT levels were determined by HPLC coupled to electrochemical detection.


RESULTS
MDMA treatment decreased tissue 5-HT in cortex, hippocampus, and caudate by about 50%. However, MDMA treatment had no significant effect on expression level of SERT and GFAP in any brain region. In contrast, 5,7-DHT reduced tissue 5-HT by more than 90%, decreased SERT protein expression by 20-35%, and increased GFAP by 30-39%.


CONCLUSIONS
These data suggest the MDMA treatment regimen used here does not cause degeneration of 5-HT nerve terminals. Viewed collectively with our previous results and other published data, these data indicate that MDMA-induced persistent 5-HT depletion may occur in the absence of axotomy.
Wang
Xiaoying
X
Clinical Psychopharmacology Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224, USA.
Baumann
Michael H
MH
Xu
Heng
H
Rothman
Richard B
RB
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects* / Q000502:physiology; D002352:Carrier Proteins / Q000187:drug effects* / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000187:drug effects* / Q000378:metabolism; D006719:Homovanillic Acid / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / 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 / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009498:Neurotoxins / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D002352:Carrier Proteins; D005904:Glial Fibrillary Acidic Protein; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D009498:Neurotoxins; D050486:Serotonin Plasma Membrane Transport Proteins; C493232:Slc6a4 protein, rat; D015102:3,4-Dihydroxyphenylacetic Acid; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D009638:Norepinephrine; D006719:Homovanillic Acid