Evidence for the involvement of nitric oxide in 3,4- methylenedioxymethamphetamine-induced serotonin depletion in the rat brain

Altaf S. Darvesh, Bryan Yamamoto, Gary A. Gudelsky

Research output: Contribution to journalArticle

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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, Nω-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.

Original languageEnglish (US)
Pages (from-to)694-701
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume312
Issue number2
DOIs
StatePublished - Feb 2005
Externally publishedYes

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N-Methyl-3,4-methylenedioxyamphetamine
Serotonin
Nitric Oxide
Brain
Dopamine
Corpus Striatum
Reactive Nitrogen Species
Amphetamine
Nitric Oxide Synthase
Perfusion
Induced Hyperthermia
Peroxynitrous Acid
Methamphetamine
Porphyrins
Arginine
Reactive Oxygen Species

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Cite this

Evidence for the involvement of nitric oxide in 3,4- methylenedioxymethamphetamine-induced serotonin depletion in the rat brain. / Darvesh, Altaf S.; Yamamoto, Bryan; Gudelsky, Gary A.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 312, No. 2, 02.2005, p. 694-701.

Research output: Contribution to journalArticle

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