Ascorbic acid prevents 3,4‐methylenedioxymethamphetamine (MDMA)‐induced hydroxyl radical formation and the behavioral and neurochemical consequences of the depletion of brain 5‐HT

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.

Oxidative Stress in Rat Retina and Hippocampus after Chronic MDMA (‘ecstasy’) Administration

“…They also showed that a-phenyl-N-tert-butyl nitrone (PBN) protected against MDMA-induced damage. Other free radical scavengers, such as sodium ascorbate, L-cysteine [12], ascorbic acid [13] or a-lipoic acid [14], also protect against MDMA-induced damage.…”

Oxidative Stress in Rat Retina and Hippocampus after Chronic MDMA (‘ecstasy’) Administration

“…They also showed that a-phenyl-N-tert-butyl nitrone (PBN) protected against MDMA-induced damage. Other free radical scavengers, such as sodium ascorbate, L-cysteine [12], ascorbic acid [13] or a-lipoic acid [14], also protect against MDMA-induced damage.…”

Effects of emodin and vitamin C on growth performance, biochemical parameters and two HSP70s mRNA expression of Wuchang bream (Megalobrama amblycephala Yih) under high temperature stress

“…The effect of Vc may be related to the antioxidant itself. It can not only eliminate free radicals directly or indirectly, but also resume the activities of glutathione peroxidase and vitamin E groups so as to revive the function of anti-free radicals [54].…”

Amphetamine-related drugs neurotoxicity in humans and in experimental animals: Main mechanisms

“…In 1996, Gudelsky first found that pretreatment with sodium ascorbate and cysteine prevented the depletion of 5-HT observed after MDMA administration in rats (Gudelsky, 1996). Similar findings were obtained by subsequent studies that found beneficial effects of -lipoic acid (Aguirre et al, 1999) and ascorbic acid (Shankaran et al, 2001) on MDMA-induced neurotoxicity.…”

Oxidative Stress in Rat Retina and Hippocampus after Chronic MDMA (‘ecstasy’) Administration

“…They also showed that a-phenyl-N-tert-butyl nitrone (PBN) protected against MDMA-induced damage. Other free radical scavengers, such as sodium ascorbate, L-cysteine [12], ascorbic acid [13] or a-lipoic acid [14], also protect against MDMA-induced damage.…”

Effects of emodin and vitamin C on growth performance, biochemical parameters and two HSP70s mRNA expression of Wuchang bream (Megalobrama amblycephala Yih) under high temperature stress

“…The effect of Vc may be related to the antioxidant itself. It can not only eliminate free radicals directly or indirectly, but also resume the activities of glutathione peroxidase and vitamin E groups so as to revive the function of anti-free radicals [54].…”

Amphetamine-related drugs neurotoxicity in humans and in experimental animals: Main mechanisms

“…In 1996, Gudelsky first found that pretreatment with sodium ascorbate and cysteine prevented the depletion of 5-HT observed after MDMA administration in rats (Gudelsky, 1996). Similar findings were obtained by subsequent studies that found beneficial effects of -lipoic acid (Aguirre et al, 1999) and ascorbic acid (Shankaran et al, 2001) on MDMA-induced neurotoxicity.…”

Oxidative Stress in Rat Retina and Hippocampus after Chronic MDMA (‘ecstasy’) Administration

“…They also showed that a-phenyl-N-tert-butyl nitrone (PBN) protected against MDMA-induced damage. Other free radical scavengers, such as sodium ascorbate, L-cysteine [12], ascorbic acid [13] or a-lipoic acid [14], also protect against MDMA-induced damage.…”

Effects of emodin and vitamin C on growth performance, biochemical parameters and two HSP70s mRNA expression of Wuchang bream (Megalobrama amblycephala Yih) under high temperature stress

“…The effect of Vc may be related to the antioxidant itself. It can not only eliminate free radicals directly or indirectly, but also resume the activities of glutathione peroxidase and vitamin E groups so as to revive the function of anti-free radicals [54].…”

Amphetamine-related drugs neurotoxicity in humans and in experimental animals: Main mechanisms

“…In 1996, Gudelsky first found that pretreatment with sodium ascorbate and cysteine prevented the depletion of 5-HT observed after MDMA administration in rats (Gudelsky, 1996). Similar findings were obtained by subsequent studies that found beneficial effects of -lipoic acid (Aguirre et al, 1999) and ascorbic acid (Shankaran et al, 2001) on MDMA-induced neurotoxicity.…”