ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2011
Genetic deletion of trace amine 1 receptors reveals their role in auto-inhibiting the actions of ecstasy (MDMA).
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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38 citing papers in PubMed, 97 citations in OpenAlex.
- Carvedilol inhibits the cardiostimulant and thermogenic effects of MDMA in humans.British journal of pharmacology · 2012Trial
- Preclinical development of [European journal of nuclear medicine and molecular imaging · 2026Article
- Wakefulness Induced by TAAR1 Partial Agonism in Mice Is Mediated Through Dopaminergic Neurotransmission.International journal of molecular sciences · 2024Article
- Wakefulness Induced by TAAR1 Partial Agonism is Mediated Through Dopaminergic Neurotransmission.bioRxiv : the preprint server for biology · 2024Article
- AlphaFold accelerated discovery of psychotropic agonists targeting the trace amine-associated receptor 1.Science advances · 2024Article
- Up-regulation of the Trace Amine Receptor, TAAR-1, in the Prefrontal Cortex of Individuals Affected by Schizophrenia.Schizophrenia bulletin · 2024Article
- Unlocking the secrets of trace amine-associated receptor 1 agonists: new horizon in neuropsychiatric treatment.Frontiers in psychiatry · 2024Review
- TAAR1 dependent and independent actions of the potential antipsychotic and dual TAAR1/5-HTNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2022Article
- Trace Amine Associate Receptor 1 (TAAR1) as a New Target for the Treatment of Cognitive Dysfunction in Alzheimer's Disease.International journal of molecular sciences · 2022Article
- Identification of a Potent Human Trace Amine-Associated Receptor 1 Antagonist.ACS chemical neuroscience · 2022Article
- Trace amine-associated receptor 1 and drug abuse.Advances in pharmacology (San Diego, Calif.) · 2022Article
- Therapeutic Potential of TAAR1 Agonists in Schizophrenia: Evidence from Preclinical Models and Clinical Studies.International journal of molecular sciences · 2021Review
- The selective TAAR1 partial agonist RO5263397 promoted novelty recognition memory in mice.Psychopharmacology · 2021Article
- Trace Amine-Associated Receptor 1 Contributes to Diverse Functional Actions of O-Phenyl-Iodotyramine in Mice but Not to the Effects of Monoamine-Based Antidepressants.International journal of molecular sciences · 2021Article
- The Pharmacological Profile of Second Generation Pyrovalerone Cathinones and Related Cathinone Derivative.International journal of molecular sciences · 2021Article
- 2-Phenylethylamine (PEA) Ameliorates Corticosterone-Induced Depression-Like Phenotype via the BDNF/TrkB/CREB Signaling Pathway.International journal of molecular sciences · 2020Article
- Differential genetic risk for methamphetamine intake confers differential sensitivity to the temperature-altering effects of other addictive drugs.Genes, brain, and behavior · 2020Article
- Designer drugs: mechanism of action and adverse effects.Archives of toxicology · 2020Review
- The Action of TAAR1 Agonist RO5263397 on Executive Functions in Rats.Cellular and molecular neurobiology · 2020Article
- The Role of Biogenic Amine Transporters in Trace Amine-Associated Receptor 1 Regulation of Methamphetamine-Induced Neurotoxicity.The Journal of pharmacology and experimental therapeutics · 2019Article
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Authors and funding
22 authors at 6 institutions in 6 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
"Ecstasy" [3,4-methylenedioxymetamphetamine (MDMA)] is of considerable interest in light of its prosocial properties and risks associated with widespread recreational use. Recently, it was found to bind trace amine-1 receptors (TA(1)Rs), which modulate dopaminergic transmission. Accordingly, using mice genetically deprived of TA(1)R (TA(1)-KO), we explored their significance to the actions of MDMA, which robustly activated human adenylyl cyclase-coupled TA(1)R transfected into HeLa cells. In wild-type (WT) mice, MDMA elicited a time-, dose-, and ambient temperature-dependent hypothermia and hyperthermia, whereas TA(1)-KO mice displayed hyperthermia only. MDMA-induced increases in dialysate levels of dopamine (DA) in dorsal striatum were amplified in TA(1)-KO mice, despite identical levels of MDMA itself. A similar facilitation of the influence of MDMA upon dopaminergic transmission was acquired in frontal cortex and nucleus accumbens, and induction of locomotion by MDMA was haloperidol-reversibly potentiated in TA(1)-KO versus WT mice. Conversely, genetic deletion of TA(1)R did not affect increases in DA levels evoked by para-chloroamphetamine (PCA), which was inactive at hTA(1) sites. The TA(1)R agonist o-phenyl-3-iodotyramine (o-PIT) blunted the DA-releasing actions of PCA both in vivo (dialysis) and in vitro (synaptosomes) in WT but not TA(1)-KO animals. MDMA-elicited increases in dialysis levels of serotonin (5-HT) were likewise greater in TA(1)-KO versus WT mice, and 5-HT-releasing actions of PCA were blunted in vivo and in vitro by o-PIT in WT mice only. In conclusion, TA(1)Rs exert an inhibitory influence on both dopaminergic and serotonergic transmission, and MDMA auto-inhibits its neurochemical and functional actions by recruitment of TA(1)R. These observations have important implications for the effects of MDMA in humans.
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