ArticleMolecular psychiatry2021
Reinstatement of synaptic plasticity in the aging brain through specific dopamine transporter inhibition.
Article in Molecular psychiatry, 2021. 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, 32 citations in OpenAlex.
- METTL3/IGF2BP1 Axis Orchestrates m6A-Dependent NCAM1 Preservation to Combat Age-Related Cognitive Decline.Cells · 2026Article
- A Series of Aryl-Substituted-(biphenyl)methyl-sulfinylmethylthiazoles as Novel and Atypical Dopamine Transporter Inhibitors.Journal of medicinal chemistry · 2026Article
- Population-level encoding of task information is stronger in the adolescent compared to adult frontal cortex.Developmental cognitive neuroscience · 2026Article
- Synaptic aging and neurodegeneration: the role of synaptic vesicle dynamics and neurotransmitter imbalance.Biogerontology · 2026Review
- The dopaminergic system in neurodevelopment: preclinical models of neurodevelopmental disorders and susceptibility to neurodegeneration.Frontiers in cellular neuroscience · 2026Review
- RDS-04-010: a novel atypical DAT inhibitor that inhibits cocaine taking and seeking and itself has low abuse potential in experimental animals.Translational psychiatry · 2025Article
- Activation of D2-like dopamine receptors improves the neuronal network and cognitive function of PPT1KI mice.Acta pharmacologica Sinica · 2025Article
- Dopamine transporter endocytic trafficking: Neuronal mechanisms and potential impact on DA-dependent behaviors.Journal of neurochemistry · 2025Review
- Series of (([1,1'-Biphenyl]-2-yl)methyl)sulfinylalkyl Alicyclic Amines as Novel and High Affinity Atypical Dopamine Transporter Inhibitors with Reduced hERG Activity.ACS pharmacology & translational science · 2024Article
- Fear extinction rescuing effects of dopamine and L-DOPA in the ventromedial prefrontal cortex.Translational psychiatry · 2024Article
- Cognitive performance in aged rats is associated with differences in distinctive neuronal populations in the ventral tegmental area and altered synaptic plasticity in the hippocampus.Frontiers in aging neuroscience · 2024Article
- The Atypical Dopamine Transporter Inhibitor CE-158 Enhances Dopamine Neurotransmission in the Prefrontal Cortex of Male Rats: A Behavioral, Electrophysiological, and Microdialysis Study.The international journal of neuropsychopharmacology · 2023Article
- Receptor-Independent Therapies for Forensic Detainees with Schizophrenia-Dementia Comorbidity.International journal of molecular sciences · 2023Article
- Chirality Matters: Fine-Tuning of Novel Monoamine Reuptake Inhibitors Selectivity through Manipulation of Stereochemistry.Biomolecules · 2023Article
- The integrity of dopaminergic and noradrenergic brain regions is associated with different aspects of late-life memory performance.Nature aging · 2023Article
- Are There Prevalent Sex Differences in Psychostimulant Use Disorder? A Focus on the Potential Therapeutic Efficacy of Atypical Dopamine Uptake Inhibitors.Molecules (Basel, Switzerland) · 2023Review
- Article
- Presynaptic Gq-coupled receptors drive biphasic dopamine transporter trafficking that modulates dopamine clearance and motor function.The Journal of biological chemistry · 2023Article
- A Novel and Selective Dopamine Transporter Inhibitor,Biomolecules · 2022Article
- Article
Corrections and comments
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Authors and funding
31 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aging-related neurological deficits negatively impact mental health, productivity, and social interactions leading to a pronounced socioeconomic burden. Since declining brain dopamine signaling during aging is associated with the onset of neurological impairments, we produced a selective dopamine transporter (DAT) inhibitor to restore endogenous dopamine levels and improve cognitive function. We describe the synthesis and pharmacological profile of (S,S)-CE-158, a highly specific DAT inhibitor, which increases dopamine levels in brain regions associated with cognition. We find both a potentiation of neurotransmission and coincident restoration of dendritic spines in the dorsal hippocampus, indicative of reinstatement of dopamine-induced synaptic plasticity in aging rodents. Treatment with (S,S)-CE-158 significantly improved behavioral flexibility in scopolamine-compromised animals and increased the number of spontaneously active prefrontal cortical neurons, both in young and aging rodents. In addition, (S,S)-CE-158 restored learning and memory recall in aging rats comparable to their young performance in a hippocampus-dependent hole board test. In sum, we present a well-tolerated, highly selective DAT inhibitor that normalizes the age-related decline in cognitive function at a synaptic level through increased dopamine signaling.
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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.