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Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on September 29, 2004; DOI: 10.1124/jpet.104.074849

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*Compound via MeSH
*Substance via MeSH
Hazardous Substances DB
*3,4-METHYLENEDIOXYMETHAMPHETAMINE
*DOPAMINE
*L-TYROSINE
*NITRIC OXIDE
*THALLOUS MALONATE
*THIOUREA
Medline Plus Health Information
*Club Drugs


Received for publication July 27, 2004.
Revised September 29, 2004.
Accepted for publication September 29, 2004.

EVIDENCE FOR THE INVOLVEMENT OF NITRIC OXIDE IN 3,4-METHYLENEDIOXYMETHAMPHETAMINE-INDUCED SEROTONIN DEPLETION IN THE RAT BRAIN

Altaf Darvesh 1, Bryan K. Yamamoto 2, Gary A. Gudelsky 1*

1 University of Cincinnati 2 Boston University School of Medicine

* Address correspondence to: E-mail: gary.gudelsky{at}uc.edu

Abstract

Production of reactive oxygen and/or nitrogen species has been thought to contribute to the long-term depletion of brain dopamine and serotonin (5-HT) produced by amphetamine derivatives, i.e. methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA). In the present study, the effects of nitric oxide synthase (NOS) inhibitors were examined on the long-term depletion of striatal dopamine and/or 5-HT produced by the local perfusion of malonate and MDMA or the systemic administration of MDMA. The effect of MDMA on nitric oxide formation and nitrotyrosine concentration also was determined. Perfusion with MDMA and malonate resulted in a 34% reduction of 5-HT and 49% reduction of dopamine concentrations in the striatum. The systemic administration of NOS inhibitors, N{omega}-nitro-L-arginine methyl ester hydrochloride and S-methyl-L-thiocitrulline (S-MTC), and the peroxynitrite decomposition catalyst Fe (III) tetrakis (1-methyl-4-pyridyl) porphyrin pentachloride attenuated the MDMA and malonate induced depletion of striatal dopamine and 5-HT. S-MTC also attenuated the depletion of 5-HT in the striatum produced by the systemic administration of MDMA without attenuating MDMA-induced hyperthermia. Additionally, the systemic administration of MDMA significantly increased the formation of nitric oxide and the nitrotyrosine concentration in the striatum. These results support the conclusion that MDMA produces reactive nitrogen species in the rat that contribute to the neurotoxicity of this amphetamine analog.


Key words: MDMA, dopamine, malonate, neurotoxicity, nitric oxide, serotonin


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B. Goni-Allo, M. Ramos, I. Herv'as, B. Lasheras, and N. Aguirre
Studies on striatal neurotoxicity caused by the 3,4-methylenedioxymethamphetamine/ malonate combination: implications for serotonin/dopamine interactions
J Psychopharmacol, March 1, 2006; 20(2): 245 - 256.
[Abstract] [PDF]


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