Restoration of 3,4-methylenedioxymethamphetamine-induced 5-HT depletion by the administration of l-5-hydroxytryptophan

@article{Wang2007RestorationO3,
  title={Restoration of 3,4-methylenedioxymethamphetamine-induced 5-HT depletion by the administration of l-5-hydroxytryptophan},
  author={Xiaoying Wang and Michael H Baumann and Christina M. Dersch and Richard B. Rothman},
  journal={Neuroscience},
  year={2007},
  volume={148},
  pages={212-220}
}
BACKGROUND 3,4-Methylenedioxymethamphetamine (MDMA) causes persistent decreases in brain 5-HT content and 5-HT transporter (SERT) binding, with no detectable changes in SERT protein. Such data suggest that MDMA impairs 5-HT transmission but leaves 5-HT nerve terminals intact. To further test this hypothesis, we carried out two types of experiments in rats exposed to high-dose MDMA. First, we examined the effects of MDMA on SERT binding and function using different in vitro assay conditions… Expand

Paper Mentions

News Article
Tolerance to 3,4-methylenedioxymethamphetamine in rats exposed to single high-dose binges
TLDR
The results suggest that MDMA tolerance in humans may reflect 5-HT deficits which could contribute to further dose escalation, and that tolerance developed only in rats exposed to high-dose binges, hyperthermia and 5- HT depletion are implicated in this phenomenon. Expand
Effects of repeated exposure to MDMA on 5HT1a autoreceptor function: behavioral and neurochemical responses to 8-OHDPAT
TLDR
The data suggest that the decrease in tissue levels of 5-HT produced by MDMA is accompanied by a decrease in tryptophan hydroxylase activity but cannot be explained by supersensitivity of the 5- HT1a autoreceptor. Expand
The Nature of 3, 4-Methylenedioxymethamphetamine (MDMA)-Induced Serotonergic Dysfunction: Evidence for and Against the Neurodegeneration Hypothesis
TLDR
The aim of this review is to address both sides of the MDMA-neurotoxicity controversy, including recent findings from the laboratory regarding the potential of MDMA to induce serotonergic damage in a rat binge model, and to add to the growing literature implicating neuroregulatory mechanisms underlying MDMA-induced Serotonergic dysfunction. Expand
Neuroadaptive Changes in5-HT1A Autoreceptor SensitivityFollowing High-Dose MDMA Treatment
TLDR
The original hypothesis that the serotonin (5-HT) deficits and related cognitive and mood impairments caused by +/-3,4methylenedioxymethamphetamine (MDMA) may be mediated by neuroadaptations of the 5-HT1A autoreceptor is not supported. Expand
Neural and cardiac toxicities associated with 3,4-methylenedioxymethamphetamine (MDMA).
TLDR
It is concluded that pharmacological effects of MDMA occur at the same doses in rats and humans, and the MDMA metabolite, 3,4-methylenedioxyamphetamine (MDA), is a potent 5-HT(2B) agonist which could contribute to the increased risk of VHD observed in heavy MDMA users. Expand
Methylenedioxymethamphetamine (MDMA, ‘Ecstasy’): Neurodegeneration versus Neuromodulation
TLDR
MDMA produces a long-lasting down-regulation of SERT gene expression, which has been used to invoke neuromodulatory mechanisms as an explanation to MDMA-induced 5-HT deficits, and decreased protein levels do not necessarily reflect neurodegeneration. Expand
Evaluating the Contribution of Serotonin Receptor Subtypes and ‘Binge’ 3,4-Methylenedioxymethamphetamine (MDMA) Exposure to the Discriminative Stimulus Effects of MDMA in Rats
3,4-Methylenedioxymethamphetamine (MDMA; ‘Ecstasy’) shares psychoactive effects with drugs that possess stimulant (e.g. amphetamine, the effects of which are primarily dopaminergic) andExpand
MDMA causes a redistribution of serotonin transporter from the cell surface to the intracellular compartment by a mechanism independent of phospho-p38-mitogen activated protein kinase activation
TLDR
It was found that p38 MAPK activation was not involved in the MDMA-induced redistribution of SERT from the cell-surface to the cell interior, which may contribute to the decreased SERT function seen in rats exposed to MDMA. Expand
Molecular and Cellular Mechanisms of Ecstasy-Induced Neurotoxicity: An Overview
TLDR
The main aim of this review was to contribute to the understanding of the cellular and molecular mechanisms involved in MDMA neurotoxicity, which can help in the development of therapeutic approaches to prevent or treat the long-term neuropsychiatric complications of MDMA abuse in humans. Expand
Identifying the serotonin transporter signal in Western blot studies of the neurotoxic potential of MDMA and related drugs
TLDR
When the band corresponding to the SERT protein is identified in Western blots through the use of positive and negative controls, reduced abundance of the Sert protein can be readily demonstrated after substituted amphetamine treatment. Expand
...
1
2
3
...

References

SHOWING 1-10 OF 35 REFERENCES
(±)-3,4-Methylenedioxymethamphetamine Administration to Rats Does Not Decrease Levels of the Serotonin Transporter Protein or Alter Its Distribution between Endosomes and the Plasma Membrane
TLDR
Findings indicate that a dosing regimen of MDMA that depletes brain 5-HT does not alter SERT protein expression or the distribution of SERT between endosomes and the plasma membrane and does not produce detectable evidence for neurotoxicity. Expand
3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings
TLDR
MDMA-induced 5- HT depletions are not necessarily synonymous with neurotoxic damage, however, doses of MDMA which do not cause long-term 5-HT depletion can have protracted effects on behavior, suggesting even moderate doses of the drug may pose risks. Expand
Effects of dexfenfluramine or 5,7-dihydroxytryptamine on tryptophan hydroxylase and serotonin transporter mRNAS in rat dorsal raphe.
TLDR
The significance of loss of forebrain markers for 5-HT reflects either the loss of fine caliber 5- HT axon terminals or a decrease in the expression of these markers in the somata of these cells which are located in the dorsal raphe. Expand
Effect of d-fenfluramine and 5,7-dihydroxytryptamine on the levels of tryptophan hydroxylase and its mRNA in rat brain.
TLDR
Repeated high doses of d-fenfluramine markedly reduced serotonin (5-HT) concentrations in the hippocampus and striatum of rat brain up to 1 month after treatment, while tryptophan hydroxylase (TPH) levels were reduced only inThe hippocampus 5 days after injection. Expand
Biochemical and histological evidence that methylenedioxymethylamphetamine (MDMA) is toxic to neurons in the rat brain.
TLDR
The findings suggest that MDMA is toxic to serotonergic and, to a lesser extent, catecholaminergic neurons and some neurons that do not contain these transmitters (neocortical neurons) are also affected. Expand
The Pharmacology and Clinical Pharmacology of 3,4-Methylenedioxymethamphetamine (MDMA, “Ecstasy”)
TLDR
Evidence for the occurrence of MDMA-induced neurotoxic damage in human users remains equivocal, although some biochemical and functional data suggest that damage may occur in the brains of heavy users. Expand
3,4‐methylenedioxymethamphetamine (MDMA) administration to rats decreases brain tissue serotonin but not serotonin transporter protein and glial fibrillary acidic protein
TLDR
The data suggest the MDMA treatment regimen used here does not cause degeneration of 5‐HT nerve terminals and indicate that MDMA‐induced persistent 5‐ HT depletion may occur in the absence of axotomy. Expand
Methylenedioxymethamphetamine-induced serotonin deficits are followed by partial recovery over a 52-week period. Part II: Radioligand binding and autoradiography studies.
TLDR
Evidence is presented showing the rate of recovery of 5-HT uptake sites varies according to region and that recovery of 3,4-methylenedioxymethamphetamine uptake sites in neocortex and hippocampus follows a rostral-caudal gradient. Expand
Methylenedioxymethamphetamine-induced serotonin deficits are followed by partial recovery over a 52-week period. Part I: Synaptosomal uptake and tissue concentrations.
TLDR
The results indicate that a high-dose MDMA regimen results in long-lasting depletions of serotonin, and the rate and degree of recovery of serotonin tissue concentrations seen over the 52-wk test period is region specific. Expand
A neurotoxic regimen of MDMA suppresses behavioral, thermal and neurochemical responses to subsequent MDMA administration
TLDR
It is concluded that the long-term depletion of brain 5-HT produced by MDMA is accompanied by impairments in 5- HT function, as evidenced by the deficits in the neurochemical, thermal and behavioral responses to subsequent MDMA administration. Expand
...
1
2
3
4
...