ArticleThe Journal of pharmacology and experimental therapeutics2009
A receptor mechanism for methamphetamine action in dopamine transporter regulation in brain.
Article in The Journal of pharmacology and experimental therapeutics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 112 citations in OpenAlex.
- Trace amine-associated receptor 1 agonists differentially regulate dopamine transporter function.Molecular pharmacology · 2025Article
- Retinal Angiogenesis in Methamphetamine Self-Administration Rats.Investigative ophthalmology & visual science · 2025Article
- Behavioral and neurophysiological signatures of cognitive control in humans and rats.The international journal of neuropsychopharmacology · 2024Article
- Molecular Mechanisms of Methamphetamine-Induced Addiction via TAAR1 Activation.Journal of medicinal chemistry · 2024Article
- Crystal methamphetamine and its effects on mental and oral health: A narrative review.The Saudi dental journal · 2024Review
- Glycine Transporter 1 Inhibitors: Predictions on Their Possible Mechanisms in the Development of Opioid Analgesic Tolerance.Biomedicines · 2024Review
- TAAR1 as an emerging target for the treatment of psychiatric disorders.Pharmacology & therapeutics · 2024Review
- Prenatal and postnatal methamphetamine exposure alters prefrontal cortical gene expression and behavior in mice.Frontiers in behavioral neuroscience · 2024Article
- The Alkylamine Stimulant 1,3-Dimethylamylamine Exhibits Substrate-Like Regulation of Dopamine Transporter Function and Localization.The Journal of pharmacology and experimental therapeutics · 2023Article
- iTat transgenic mice exhibit hyper-locomotion in the behavioral pattern monitor after chronic exposure to methamphetamine but are unaffected by Tat expression.Pharmacology, biochemistry, and behavior · 2023Article
- Neuroprotective Effects of Selegiline Agent Methamphetamine-Prompted Mood-Related Behavior Disorder Mediated Via 5-HTInternational journal of preventive medicine · 2023Article
- Enhancer Regulation of Dopaminergic Neurochemical Transmission in the Striatum.International journal of molecular sciences · 2022Article
- Trace amine-associated receptor 1 and drug abuse.Advances in pharmacology (San Diego, Calif.) · 2022Article
- Methamphetamine Dysregulation of the Central Nervous System and Peripheral Immunity.The Journal of pharmacology and experimental therapeutics · 2021Review
- Aiding and Abetting Anhedonia: Impact of Inflammation on the Brain and Pharmacological Implications.Pharmacological reviews · 2021Review
- Amphetamines signal through intracellular TAAR1 receptors coupled to GαMolecular psychiatry · 2021Article
- Psychostimulant Use Disorder, an Unmet Therapeutic Goal: Can Modafinil Narrow the Gap?Frontiers in neuroscience · 2021Review
- No Association Between AKT1 Polymorphisms and Methamphetamine Addiction in Iranian Population.Journal of molecular neuroscience : MN · 2020Article
- TAAR1 and Psychostimulant Addiction.Cellular and molecular neurobiology · 2020Review
- A prior history of binge-drinking increases sensitivity to the motivational valence of methamphetamine in female C57BL/6J mice.Substance abuse : research and treatment · 2020Article
1 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
This study reveals a novel receptor mechanism for methamphetamine action in dopamine transporter (DAT) regulation. Trace amine-associated receptor 1 (TAAR1) is expressed in brain dopaminergic nuclei and is activated by methamphetamine in vitro. Here, we show that methamphetamine interaction with TAAR1 inhibits [(3)H]dopamine uptake, enhances or induces [(3)H]dopamine efflux, and triggers DAT internalization. In time course assays in which methamphetamine and [(3)H]dopamine were concurrently loaded into cells or synaptosomes or in pretreatment assays in which methamphetamine was washed away before [(3)H]dopamine loading, methamphetamine caused a distinct inhibition in [(3)H]dopamine uptake in TAAR1 + DAT-cotransfected cells and in wild-type mouse and rhesus monkey striatal synaptosomes. This distinct uptake inhibition was not observed in DAT-only transfected cells or in TAAR1 knockout mouse striatal synaptosomes. In [(3)H]dopamine efflux assays using the same cell and synaptosome preparations, methamphetamine enhanced [(3)H]dopamine efflux at a high loading concentration of [(3)H]dopamine (1 muM) or induced [(3)H]dopamine efflux at a low loading concentration of [(3)H]dopamine (10 nM) in a TAAR1-dependent manner. In DAT biotinylation assays using the same cell and synaptosome preparations, we observed that 1 muM methamphetamine induced DAT internalization in a TAAR1-dependent manner. All these TAAR1-mediated effects of methamphetamine were blocked by the protein kinase inhibitors H89 [N-[2-(4-bromocinnamylamino)ethyl]-5-isoquinoline] and/or 2-{8-[(dimethylamino) methyl]-6,7,8,9-tetrahydropyrido[1,2-a]indol-3-yl}-3-(1-methylindol-3-yl)maleimide (Ro32-0432), suggesting that methamphetamine interaction with TAAR1 triggers cellular phosphorylation cascades and leads to the observed effects of methamphetamine on DAT. These findings demonstrate a mediatory role of TAAR1 in methamphetamine action in DAT regulation and implicate this receptor as a potential target of therapeutics drugs for methamphetamine addiction.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.