ArticleProceedings of the National Academy of Sciences of the United States of America2000
Amplification of dopaminergic signaling by a positive feedback loop.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
86 citing papers in PubMed, 1 synthesis or guideline pooled it, 235 citations in OpenAlex.
- The Signaling and Pharmacology of the Dopamine D1 Receptor.Frontiers in cellular neuroscience · 2021Pooled it
- Identifying key transcription factors for pharmacogenetic studies of antipsychotics induced extrapyramidal symptoms.Psychopharmacology · 2020Trial
- Optogenetic Control of Dopamine Receptor 2 Reveals a Novel Aspect of Dopaminergic Neurotransmission in Motor Function.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Neuromodulator regulation and emotions: insights from the crosstalk of cell signaling.Frontiers in molecular neuroscience · 2024Review
- Phosphodiesterase-4 Inhibition in Parkinson's Disease: Molecular Insights and Therapeutic Potential.Cellular and molecular neurobiology · 2023Review
- Article
- Systemic Administration of a Brain Permeable Cdk5 Inhibitor Alters Neurobehavior.Frontiers in pharmacology · 2022Article
- Functional metabolomics reveal the role of AHR/GPR35 mediated kynurenic acid gradient sensing in chemotherapy-induced intestinal damage.Acta pharmaceutica Sinica. B · 2021Article
- Article
- Effects of nicotine on DARPP-32 and CaMKII signaling relevant to addiction.Advances in pharmacology (San Diego, Calif.) · 2021Review
- Novel Diels-Alder Type Adducts fromInternational journal of molecular sciences · 2019Article
- cAMP regulation of protein phosphatases PP1 and PP2A in brain.Biochimica et biophysica acta. Molecular cell research · 2019Review
- Sucrose Abstinence and Environmental Enrichment Effects on Mesocorticolimbic DARPP32 in Rats.Scientific reports · 2018Article
- Neuroanatomic, epigenetic and genetic differences in monozygotic twins discordant for attention deficit hyperactivity disorder.Molecular psychiatry · 2018Article
- Epigenetic Effects Induced by Methamphetamine and Methamphetamine-Dependent Oxidative Stress.Oxidative medicine and cellular longevity · 2018Review
- Detection of phasic dopamine by D1 and D2 striatal medium spiny neurons.The Journal of physiology · 2017Article
- ARPP-16 Is a Striatal-Enriched Inhibitor of Protein Phosphatase 2A Regulated by Microtubule-Associated Serine/Threonine Kinase 3 (Mast 3 Kinase).The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- Glutamate Counteracts Dopamine/PKA Signaling via Dephosphorylation of DARPP-32 Ser-97 and Alteration of Its Cytonuclear Distribution.The Journal of biological chemistry · 2017Article
- Activation of Dopamine D1-D2 Receptor Complex Attenuates Cocaine Reward and Reinstatement of Cocaine-Seeking through Inhibition of DARPP-32, ERK, and ΔFosB.Frontiers in pharmacology · 2017Article
- Neuronal circuits and physiological roles of the basal ganglia in terms of transmitters, receptors and related disorders.The journal of physiological sciences : JPS · 2016Review
26 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Dopamine and cAMP-regulated phosphoprotein of M(r) 32,000 (DARPP-32) plays an obligatory role in most of the actions of dopamine. In resting neostriatal slices, cyclin-dependent kinase 5 (Cdk5) phosphorylates DARPP-32 at Thr-75, thereby reducing the efficacy of dopaminergic signaling. We report here that dopamine, in slices, and acute cocaine, in whole animals, decreases the state of phosphorylation of striatal DARPP-32 at Thr-75 and thereby removes this inhibitory constraint. This effect of dopamine is achieved through dopamine D1 receptor-mediated activation of cAMP-dependent protein kinase (PKA). The activated PKA, by decreasing the state of phosphorylation of DARPP-32-Thr-75, de-inhibits itself. Dopamine D2 receptor stimulation has the opposite effect. The ability of activated PKA to reduce the state of phosphorylation of DARPP-32-Thr-75 is apparently attributable to increased protein phosphatase-2A activity, with Cdk5 being unaffected. Together, these results indicate that via positive feedback mechanisms, Cdk5 signaling and PKA signaling are mutually antagonistic.
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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.