Ascorbic acid prevents 3,4-methylenedioxymethamphetamine (MDMA)-induced hydroxyl radical formation and the behavioral and neurochemical consequences of the depletion of brain 5-HT
Article first published online: 6 FEB 2001
Copyright © 2001 Wiley-Liss, Inc.
Volume 40, Issue 1, pages 55–64, April 2001
How to Cite
Shankaran, M., Yamamoto, B. K. and 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, 40: 55–64. doi: 10.1002/1098-2396(200104)40:1<55::AID-SYN1026>3.0.CO;2-O
- Issue published online: 6 FEB 2001
- Article first published online: 6 FEB 2001
- Manuscript Accepted: 23 AUG 2000
- Manuscript Received: 26 APR 2000
- National Institute on Drug Abuse. Grant Number: USPHS DA 07427
- hydroxyl radicals
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. Synapse 40:55–64, 2001. © 2001 Wiley-Liss, Inc.