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3,4-methylenedioxymethamphetamine (MDMA) administration to rats decreases brain tissue serotonin but not serotonin transporter protein and glial fibrillary acidic protein.
Synapse 2004; 53(4):240-8S

Abstract

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.

HYPOTHESIS

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%.

CONCLUSION

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.

Authors+Show Affiliations

Clinical Psychopharmacology Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

15266556

Citation

Wang, Xiaoying, et al. "3,4-methylenedioxymethamphetamine (MDMA) Administration to Rats Decreases Brain Tissue Serotonin but Not Serotonin Transporter Protein and Glial Fibrillary Acidic Protein." Synapse (New York, N.Y.), vol. 53, no. 4, 2004, pp. 240-8.
Wang X, Baumann MH, Xu H, et al. 3,4-methylenedioxymethamphetamine (MDMA) administration to rats decreases brain tissue serotonin but not serotonin transporter protein and glial fibrillary acidic protein. Synapse. 2004;53(4):240-8.
Wang, X., Baumann, M. H., Xu, H., & Rothman, R. B. (2004). 3,4-methylenedioxymethamphetamine (MDMA) administration to rats decreases brain tissue serotonin but not serotonin transporter protein and glial fibrillary acidic protein. Synapse (New York, N.Y.), 53(4), pp. 240-8.
Wang X, et al. 3,4-methylenedioxymethamphetamine (MDMA) Administration to Rats Decreases Brain Tissue Serotonin but Not Serotonin Transporter Protein and Glial Fibrillary Acidic Protein. Synapse. 2004 Sep 15;53(4):240-8. PubMed PMID: 15266556.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 3,4-methylenedioxymethamphetamine (MDMA) administration to rats decreases brain tissue serotonin but not serotonin transporter protein and glial fibrillary acidic protein. AU - Wang,Xiaoying, AU - Baumann,Michael H, AU - Xu,Heng, AU - Rothman,Richard B, PY - 2004/7/22/pubmed PY - 2004/11/13/medline PY - 2004/7/22/entrez SP - 240 EP - 8 JF - Synapse (New York, N.Y.) JO - Synapse VL - 53 IS - 4 N2 - UNLABELLED: 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. HYPOTHESIS: 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%. CONCLUSION: 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. SN - 0887-4476 UR - https://www.unboundmedicine.com/medline/citation/15266556/34_methylenedioxymethamphetamine__MDMA__administration_to_rats_decreases_brain_tissue_serotonin_but_not_serotonin_transporter_protein_and_glial_fibrillary_acidic_protein_ L2 - https://doi.org/10.1002/syn.20058 DB - PRIME DP - Unbound Medicine ER -