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Ascorbic acid prevents 3,4-methylenedioxymethamphetamine (MDMA)-induced hydroxyl radical formation and the behavioral and neurochemical consequences of the depletion of brain 5-HT.
Synapse. 2001 Apr; 40(1):55-64.S

Abstract

MDMA-induced 5-HT neurotoxicity has been proposed to involve oxidative stress due to increased formation of hydroxyl radicals. Recently, MDMA-induced 5-HT neurotoxicity has been shown to be accompanied by a suppression of behavioral and neurochemical responses to a subsequent injection of MDMA. The intent of the present study was to examine whether suppression of the MDMA-induced formation of hydroxyl radicals by an antioxidant, ascorbic acid, attenuates both the MDMA-induced depletion of 5-HT and the functional consequences associated with this depletion. Treatment of rats with ascorbic acid suppressed the generation of hydroxyl radicals, as evidenced by the production of 2,3-dihydroxybenzoic acid from salicylic acid, in the striatum during the administration of a neurotoxic regimen of MDMA. Ascorbic acid also attenuated the MDMA-induced depletion of striatal 5-HT content. In rats treated with a neurotoxic regimen of MDMA, the ability of a subsequent injection of MDMA to increase the extracellular concentration of 5-HT in the striatum, elicit the 5-HT behavioral syndrome, and produce hyperthermia was markedly reduced compared to the responses in control rats. The concomitant administration of ascorbic acid with the neurotoxic regimen of MDMA prevented the diminished neurochemical and behavioral responses to a subsequent injection of MDMA. Finally, a neurotoxic regimen of MDMA produced significant reductions in the concentrations of vitamin E and ascorbic acid in the striatum and hippocampus. Thus, the MDMA-induced depletion of brain 5-HT and the functional consequences thereof appear to involve the induction of oxidative stress resulting from an increased generation of free radicals and diminished antioxidant capacity of the brain.

Authors+Show Affiliations

College of Pharmacy, University of Cincinnati, Cincinnati, Ohio 45267-0004, 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

11170222

Citation

Shankaran, M, et al. "Ascorbic Acid Prevents 3,4-methylenedioxymethamphetamine (MDMA)-induced Hydroxyl Radical Formation and the Behavioral and Neurochemical Consequences of the Depletion of Brain 5-HT." Synapse (New York, N.Y.), vol. 40, no. 1, 2001, pp. 55-64.
Shankaran M, Yamamoto BK, Gudelsky GA. Ascorbic acid prevents 3,4-methylenedioxymethamphetamine (MDMA)-induced hydroxyl radical formation and the behavioral and neurochemical consequences of the depletion of brain 5-HT. Synapse. 2001;40(1):55-64.
Shankaran, M., Yamamoto, B. K., & Gudelsky, G. A. (2001). Ascorbic acid prevents 3,4-methylenedioxymethamphetamine (MDMA)-induced hydroxyl radical formation and the behavioral and neurochemical consequences of the depletion of brain 5-HT. Synapse (New York, N.Y.), 40(1), 55-64.
Shankaran M, Yamamoto BK, Gudelsky GA. Ascorbic Acid Prevents 3,4-methylenedioxymethamphetamine (MDMA)-induced Hydroxyl Radical Formation and the Behavioral and Neurochemical Consequences of the Depletion of Brain 5-HT. Synapse. 2001;40(1):55-64. PubMed PMID: 11170222.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ascorbic acid prevents 3,4-methylenedioxymethamphetamine (MDMA)-induced hydroxyl radical formation and the behavioral and neurochemical consequences of the depletion of brain 5-HT. AU - Shankaran,M, AU - Yamamoto,B K, AU - Gudelsky,G A, PY - 2001/2/15/pubmed PY - 2001/5/5/medline PY - 2001/2/15/entrez SP - 55 EP - 64 JF - Synapse (New York, N.Y.) JO - Synapse VL - 40 IS - 1 N2 - MDMA-induced 5-HT neurotoxicity has been proposed to involve oxidative stress due to increased formation of hydroxyl radicals. Recently, MDMA-induced 5-HT neurotoxicity has been shown to be accompanied by a suppression of behavioral and neurochemical responses to a subsequent injection of MDMA. The intent of the present study was to examine whether suppression of the MDMA-induced formation of hydroxyl radicals by an antioxidant, ascorbic acid, attenuates both the MDMA-induced depletion of 5-HT and the functional consequences associated with this depletion. Treatment of rats with ascorbic acid suppressed the generation of hydroxyl radicals, as evidenced by the production of 2,3-dihydroxybenzoic acid from salicylic acid, in the striatum during the administration of a neurotoxic regimen of MDMA. Ascorbic acid also attenuated the MDMA-induced depletion of striatal 5-HT content. In rats treated with a neurotoxic regimen of MDMA, the ability of a subsequent injection of MDMA to increase the extracellular concentration of 5-HT in the striatum, elicit the 5-HT behavioral syndrome, and produce hyperthermia was markedly reduced compared to the responses in control rats. The concomitant administration of ascorbic acid with the neurotoxic regimen of MDMA prevented the diminished neurochemical and behavioral responses to a subsequent injection of MDMA. Finally, a neurotoxic regimen of MDMA produced significant reductions in the concentrations of vitamin E and ascorbic acid in the striatum and hippocampus. Thus, the MDMA-induced depletion of brain 5-HT and the functional consequences thereof appear to involve the induction of oxidative stress resulting from an increased generation of free radicals and diminished antioxidant capacity of the brain. SN - 0887-4476 UR - https://www.unboundmedicine.com/medline/citation/11170222/Ascorbic_acid_prevents_34_methylenedioxymethamphetamine__MDMA__induced_hydroxyl_radical_formation_and_the_behavioral_and_neurochemical_consequences_of_the_depletion_of_brain_5_HT_ L2 - https://doi.org/10.1002/1098-2396(200104)40:1<55::AID-SYN1026>3.0.CO;2-O DB - PRIME DP - Unbound Medicine ER -