ArticlePloS one2012
Dopamine transporter loss in 6-OHDA Parkinson's model is unmet by parallel reduction in dopamine uptake.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 58 citations in OpenAlex.
- Neuroprotective Effects of Lycopene in Parkinson's Disease Mice: Potential Modulation of DAT/SLC6A3-Mediated Dopaminergic Pathway.Nutrients · 2026Article
- Preservation of Extracellular and Tissue Dopamine During Tyrosine Hydroxylase Loss in Rat 6-OHDA Parkinson's Model: Selective Compensation Restricted to Substantia Nigra.International journal of molecular sciences · 2026Article
- Monoamine Oxidase Inhibitors in Toxic Models of Parkinsonism.International journal of molecular sciences · 2025Review
- The chronic use of serotonin norepinephrine reuptake inhibitors facilitates dyskinesia priming in early Parkinson's disease.Journal of neurology · 2024Article
- Experimental Models to Study Immune Dysfunction in the Pathogenesis of Parkinson's Disease.International journal of molecular sciences · 2024Review
- Dopamine Signaling in Substantia Nigra and Its Impact on Locomotor Function-Not a New Concept, but Neglected Reality.International journal of molecular sciences · 2024Review
- Consequences of Acute or Chronic Methylphenidate Exposure Using Ex Vivo Neurochemistry and In Vivo Electrophysiology in the Prefrontal Cortex and Striatum of Rats.International journal of molecular sciences · 2022Article
- Evaluation of 6-Hydroxydopamine and Rotenone In Vitro Neurotoxicity on Differentiated SH-SY5Y Cells Using Applied Computational Statistics.International journal of molecular sciences · 2022Article
- Multifactoriality of Parkinson's Disease as Explored Through Human Neural Stem Cells and Their Transplantation in Middle-Aged Parkinsonian Mice.Frontiers in pharmacology · 2021Article
- Behavioral Tests in Neurotoxin-Induced Animal Models of Parkinson's Disease.Antioxidants (Basel, Switzerland) · 2020Review
- Diabetes Causes Dysfunctional Dopamine Neurotransmission Favoring Nigrostriatal Degeneration in Mice.Movement disorders : official journal of the Movement Disorder Society · 2020Article
- The Noradrenergic System in Parkinson's Disease.Frontiers in pharmacology · 2020Review
- 2-Pentadecyl-2-Oxazoline Reduces Neuroinflammatory Environment in the MPTP Model of Parkinson Disease.Molecular neurobiology · 2018Article
- Vitamin D protects dopaminergic neurons against neuroinflammation and oxidative stress in hemiparkinsonian rats.Journal of neuroinflammation · 2018Article
- Degree of dopaminergic degeneration measured byNeural regeneration research · 2018Article
- Ceftriaxone reduces L-dopa-induced dyskinesia severity in 6-hydroxydopamine parkinson's disease model.Movement disorders : official journal of the Movement Disorder Society · 2017Article
- What Mechanisms Are Responsible for the Reuptake of Levodopa-Derived Dopamine in Parkinsonian Striatum?Frontiers in neuroscience · 2016Review
- Pyrylium Salts as Reactive Matrices for MALDI-MS Imaging of Biologically Active Primary Amines.Journal of the American Society for Mass Spectrometry · 2015Article
- Ceftriaxone increases glutamate uptake and reduces striatal tyrosine hydroxylase loss in 6-OHDA Parkinson's model.Molecular neurobiology · 2014Article
- ser31 Tyrosine hydroxylase phosphorylation parallels differences in dopamine recovery in nigrostriatal pathway following 6-OHDA lesion.Journal of neurochemistry · 2014Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The dopamine transporter (DAT) regulates synaptic dopamine (DA) in striatum and modulation of DAT can affect locomotor activity. Thus, in Parkinson's disease (PD), DAT loss could affect DA clearance and locomotor activity. The locomotor benefits of L-DOPA may be mediated by transport through monoamine transporters and conversion to DA. However, its impact upon DA reuptake is unknown and may modulate synaptic DA. Using the unilateral 6-OHDA rat PD model, we examined [(3)H]DA uptake dynamics in relation to striatal DAT and tyrosine hydroxylase (TH) protein loss compared with contralateral intact striatum. Despite >70% striatal DAT loss, DA uptake decreased only ∼25% and increased as DAT loss approached 99%. As other monoamine transporters can transport DA, we determined if norepinephrine (NE) and serotonin (5-HT) differentially modulated DA uptake in lesioned striatum. Unlabeled DA, NE, and 5-HT were used, at a concentration that differentially inhibited DA uptake in intact striatum, to compete against [(3)H]DA uptake. In 6-OHDA lesioned striatum, DA was less effective, whereas NE was more effective, at inhibiting [(3)H]DA uptake. Furthermore, norepinephrine transporter (NET) protein levels increased and desipramine was ∼two-fold more effective at inhibiting NE uptake. Serotonin inhibited [(3)H]DA uptake, but without significant difference between lesioned and contralateral striatum. L-DOPA inhibited [(3)H]DA uptake two-fold more in lesioned striatum and inhibited NE uptake ∼five-fold more than DA uptake in naïve striatum. Consequently, DA uptake may be mediated by NET when DAT loss is at PD levels. Increased inhibition of DA uptake by L-DOPA and its preferential inhibition of NE over DA uptake, indicates that NET-mediated DA uptake may be modulated by L-DOPA when DAT loss exceeds 70%. These results indicate a novel mechanism for DA uptake during PD progression and provide new insight into how L-DOPA affects DA uptake, revealing possible mechanisms of its therapeutic and side effect potential.
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