ArticleJournal of neurochemistry2008
Pregnenolone sulfate induces NMDA receptor dependent release of dopamine from synaptic terminals in the striatum.
Article in Journal of neurochemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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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.
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Who cites it
18 citing papers in PubMed, 28 citations in OpenAlex.
- The role of neuroactive steroids in psychiatric and neurological disorders: Neurobiology and therapeutic perspectives.Neuroscience and biobehavioral reviews · 2025Review
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- Neurosteroids: a lifelong impact on brain health.Frontiers in behavioral neuroscience · 2025Review
- Apoptosis signal-regulating kinase 1 (Frontiers in cellular neuroscience · 2024Article
- Presynaptic release-regulating NMDA receptors in isolated nerve terminals: A narrative review.British journal of pharmacology · 2021Review
- Neuropsychiatric phenotype in relation to gene variants in the hemizygous allele in 3q29 deletion carriers: A case series.Molecular genetics & genomic medicine · 2019Article
- Baicalin regulates the dopamine system to control the core symptoms of ADHD.Molecular brain · 2019Article
- Neurosteroid Actions in Memory and Neurologic/Neuropsychiatric Disorders.Frontiers in endocrinology · 2019Review
- Calcium-engaged Mechanisms of Nongenomic Action of Neurosteroids.Current neuropharmacology · 2017Review
- A role for picomolar concentrations of pregnenolone sulfate in synaptic activity-dependent Ca2+ signaling and CREB activation.Molecular pharmacology · 2014Article
- Pregnenolone sulfate as a modulator of synaptic plasticity.Psychopharmacology · 2014Review
- Pregnenolone sulfate: from steroid metabolite to TRP channel ligand.Molecules (Basel, Switzerland) · 2013Review
- The neuroactive steroid pregnenolone sulfate stimulates trafficking of functional N-methyl D-aspartate receptors to the cell surface via a noncanonical, G protein, and Ca2+-dependent mechanism.Molecular pharmacology · 2013Article
- Modifications of neuroactive steroid levels in an experimental model of nigrostriatal degeneration: potential relevance to the pathophysiology of Parkinson's disease.Journal of molecular neuroscience : MN · 2012Article
- Pregnenolone rescues schizophrenia-like behavior in dopamine transporter knockout mice.PloS one · 2012Article
- A steroid modulatory domain in NR2A collaborates with NR1 exon-5 to control NMDAR modulation by pregnenolone sulfate and protons.Journal of neurochemistry · 2011Article
- Presynaptic NMDA Receptors and Spike Timing-Dependent Depression at Cortical Synapses.Frontiers in synaptic neuroscience · 2010Article
- Nanomolar concentrations of pregnenolone sulfate enhance striatal dopamine overflow in vivo.The Journal of pharmacology and experimental therapeutics · 2008Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Neuromodulators that alter the balance between lower-frequency glutamate-mediated excitatory and higher-frequency GABA-mediated inhibitory synaptic transmission are likely to participate in core mechanisms for CNS function and may contribute to the pathophysiology of neurological disorders such as schizophrenia and Alzheimer's disease. Pregnenolone sulfate (PS) modulates both ionotropic glutamate and GABA(A) receptor mediated synaptic transmission. The enzymes necessary for PS synthesis and degradation are found in brain tissue of several species including human and rat, and up to 5 nM PS has been detected in extracts of postmortem human brain. Here, we ask whether PS could modulate transmitter release from nerve terminals located in the striatum. Superfusion of a preparation of striatal nerve terminals comprised of mixed synaptosomes and synaptoneurosomes with brief-duration (2 min) pulses of 25 nM PS demonstrates that PS increases the release of newly accumulated [3H]dopamine ([3H]DA), but not [14C]glutamate or [3H]GABA, whereas pregnenolone is without effect. PS does not affect dopamine transporter (DAT) mediated uptake of [3H]DA, demonstrating that it specifically affects the transmitter release mechanism. The PS-induced [3H]DA release occurs via an NMDA receptor (NMDAR) dependent mechanism as it is blocked by D-2-amino-5-phosphonovaleric acid. PS modulates DA release with very high potency, significantly increasing [3H]DA release at PS concentrations as low as 25 pM. This first report of a selective direct enhancement of synaptosomal dopamine release by PS at picomolar concentrations via an NMDAR dependent mechanism raises the possibility that dopaminergic axon terminals may be a site of action for this neurosteroid.
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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.