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Evidence for the involvement of nitric oxide in 3,4-methylenedioxymethamphetamine-induced serotonin depletion in the rat brain.
J Pharmacol Exp Ther. 2005 Feb; 312(2):694-701.JP

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.

Authors+Show Affiliations

University of Cincinnati, College of Pharmacy, 3223 Eden Ave., Cincinnati, OH 45267, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15456837

Citation

Darvesh, Altaf S., et al. "Evidence for the Involvement of Nitric Oxide in 3,4-methylenedioxymethamphetamine-induced Serotonin Depletion in the Rat Brain." The Journal of Pharmacology and Experimental Therapeutics, vol. 312, no. 2, 2005, pp. 694-701.
Darvesh AS, Yamamoto BK, Gudelsky GA. Evidence for the involvement of nitric oxide in 3,4-methylenedioxymethamphetamine-induced serotonin depletion in the rat brain. J Pharmacol Exp Ther. 2005;312(2):694-701.
Darvesh, A. S., Yamamoto, B. K., & Gudelsky, G. A. (2005). Evidence for the involvement of nitric oxide in 3,4-methylenedioxymethamphetamine-induced serotonin depletion in the rat brain. The Journal of Pharmacology and Experimental Therapeutics, 312(2), 694-701.
Darvesh AS, Yamamoto BK, Gudelsky GA. Evidence for the Involvement of Nitric Oxide in 3,4-methylenedioxymethamphetamine-induced Serotonin Depletion in the Rat Brain. J Pharmacol Exp Ther. 2005;312(2):694-701. PubMed PMID: 15456837.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Evidence for the involvement of nitric oxide in 3,4-methylenedioxymethamphetamine-induced serotonin depletion in the rat brain. AU - Darvesh,Altaf S, AU - Yamamoto,Bryan K, AU - Gudelsky,Gary A, Y1 - 2004/09/29/ PY - 2004/10/1/pubmed PY - 2005/3/19/medline PY - 2004/10/1/entrez SP - 694 EP - 701 JF - The Journal of pharmacology and experimental therapeutics JO - J. Pharmacol. Exp. Ther. VL - 312 IS - 2 N2 - 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. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/15456837/Evidence_for_the_involvement_of_nitric_oxide_in_34_methylenedioxymethamphetamine_induced_serotonin_depletion_in_the_rat_brain_ L2 - http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=15456837 DB - PRIME DP - Unbound Medicine ER -