ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2006
L-tyrosine contributes to (+)-3,4-methylenedioxymethamphetamine-induced serotonin depletions.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 40 citations in OpenAlex.
- Integrated omics revealed the altered colonic microenvironment after inhibition of peripheral serotonin synthesis by LP533401.iMetaOmics · 2024Article
- L-Tyrosine availability affects basal and stimulated catecholamine indices in prefrontal cortex and striatum of the rat.Neuropharmacology · 2017Article
- Binge ethanol withdrawal: Effects on post-withdrawal ethanol intake, glutamate-glutamine cycle and monoamine tissue content in P rat model.Behavioural brain research · 2016Article
- Ceftriaxone attenuates ethanol drinking and restores extracellular glutamate concentration through normalization of GLT-1 in nucleus accumbens of male alcohol-preferring rats.Neuropharmacology · 2015Article
- Vesicular monoamine transporter 2 and the acute and long-term response to 3,4-(±)-methylenedioxymethamphetamine.Toxicological sciences : an official journal of the Society of Toxicology · 2015Article
- 3,4-methylenedioxymethamphetamine induces gene expression changes in rats related to serotonergic and dopaminergic systems, but not to neurotoxicity.Neurotoxicity research · 2014Article
- Resveratrol attenuates L-DOPA-induced hydrogen peroxide toxicity in neuronal cells.Neuroreport · 2012Article
- Peripheral ammonia as a mediator of methamphetamine neurotoxicity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2012Article
- Lost in translation: preclinical studies on 3,4-methylenedioxymethamphetamine provide information on mechanisms of action, but do not allow accurate prediction of adverse events in humans.British journal of pharmacology · 2012Review
- 5-HTP efficacy and contraindications.Neuropsychiatric disease and treatment · 2012Article
- Chronic administration of THC prevents the behavioral effects of intermittent adolescent MDMA administration and attenuates MDMA-induced hyperthermia and neurotoxicity in rats.Neuropharmacology · 2011Article
- Serotonin 2 receptor modulation of hyperthermia, corticosterone, and hippocampal serotonin depletions following serial exposure to chronic stress and methamphetamine.Psychoneuroendocrinology · 2010Article
- Amphetamine toxicities: classical and emerging mechanisms.Annals of the New York Academy of Sciences · 2010Review
- Direct and decarboxylation-dependent effects of neurotransmitter precursors on firing of isolated monoaminergic neurons.Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology · 2009Article
- Molecular and cellular mechanisms of ecstasy-induced neurotoxicity: an overview.Molecular neurobiology · 2009Review
- The role of oxidative stress, metabolic compromise, and inflammation in neuronal injury produced by amphetamine-related drugs of abuse.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2008Review
- Actions of 3,4-methylenedioxymethamphetamine (MDMA) on cerebral dopaminergic, serotonergic and cholinergic neurons.Pharmacology, biochemistry, and behavior · 2008Review
- The relationship between core body temperature and 3,4-methylenedioxymethamphetamine metabolism in rats: implications for neurotoxicity.Psychopharmacology · 2008Article
- Comparative potencies of 3,4-methylenedioxymethamphetamine (MDMA) analogues as inhibitors of [3H]noradrenaline and [3H]5-HT transport in mammalian cell lines.British journal of pharmacology · 2007Article
- MDMA-induced neurotoxicity: long-term effects on 5-HT biosynthesis and the influence of ambient temperature.British journal of pharmacology · 2006Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The specific mechanisms underlying (+)-3,4-methylenedioxymethamphetamine (MDMA)-induced damage to 5-HT terminals are unknown. Despite the hypothesized role for dopamine (DA) and DA-derived free radicals in mediating this damage, it remains unclear why MDMA produces long-term depletions of 5-HT in brain regions that are sparsely innervated by DA neurons. We hypothesized that the precursor to DA biosynthesis, tyrosine, mediates MDMA-induced 5-HT depletions. Extracellular tyrosine concentrations increased fivefold in striatum and 2.5-fold in hippocampus during the administration of neurotoxic doses of MDMA. In vitro results show that L-tyrosine can be hydroxylated nonenzymatically to the DA precursor l-3,4-dihydroxyphenylalanine (DOPA) under pro-oxidant conditions. The local infusion of L-tyrosine into the striatum or hippocampus during MDMA administration potentiated the acute increase in extracellular DA and the long-term depletion of 5-HT after MDMA. Coinfusion of the aromatic amino acid decarboxylase (AADC) inhibitor m-hydroxybenzylhydrazine attenuated these effects in hippocampus and decreased basal extracellular DA in the striatum. In contrast, the reverse dialysis of the tyrosine hydroxylase inhibitor alpha-methyl-p-tyrosine into the hippocampus did not affect MDMA-induced increases in extracellular DA or the long-term depletion in 5-HT. These results show that MDMA increases the concentration of tyrosine in the brain to cause a long-term depletion of 5-HT via the nonenzymatic, tyrosine hydroxylase-independent, hydroxylation of tyrosine to DOPA and subsequently to DA via AADC. Overall, the findings suggest that MDMA depletes 5-HT by increasing tyrosine and its eventual conversion to DA within 5-HT terminals.
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