Ascorbic acid prevents 3,4-methylenedioxymethamphetamine (MDMA)-induced hydroxyl radical formation and the behavioral and neurochemical consequences of the depletion of brain 5-HT
Mahalakshmi Shankaran, Bryan K. Yamamoto, Gary A. Gudelsky
Synapse 2001 DOI: 10.1002/1098-2396(200104)40:1<55::aid-syn1026>3.0.co;2-o (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | MDMA ascorbic acid |
| Topics | MDMA Serotonin |
| Keywords | Ascorbic acid Neurochemical Neurotoxicity Striatum Pharmacology Oxidative stress Hippocampus Dopamine |
| Citations | 97 |
| Key findings | Ascorbic acid suppressed MDMA-induced hydroxyl radical formation and serotonin depletion in the rat striatum and prevented the reduced neurochemical and behavioral responses to a subsequent MDMA injection. |
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.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 28
- The Role of Metabolism in 3,4-(±)-Methylenedioxyamphetamine and 3,4-(±)-Methylenedioxymethamphetamine (Ecstasy) toxicity Therapeutic Drug Monitoring March 19, 2004
- MDMA Increases Glutamate Release and Reduces Parvalbumin-Positive GABAergic Cells in the Dorsal Hippocampus of the Rat: Role of Cyclooxygenase Journal of Neuroimmune Pharmacology November 17, 2012
- 3,4-Methylenedioxymethamphetamine (MDMA) Abuse may Cause Oxidative Stress and Potential Free Radical Damage Free Radical Research 2003
- (±)3,4-methylenedioxymethamphetamine ("ecstasy") treatment modulates expression of neurotrophins and their receptors in multiple regions of adult rat brain. The Journal of Comparative Neurology August 1, 2012
- A PET study of effects of chronic 3,4‐methylenedioxymethamphetamine (MDMA, “ecstasy”) on serotonin markers in Göttingen minipig brain Synapse April 5, 2007
and 23 more in the library
Cites 25
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- Reducedin vivobinding to the serotonin transporter in the cerebral cortex of MDMA (‘ecstasy’) users The British Journal of Psychiatry July 1, 1999
and 20 more in the library