Journal article
Dopamine transporters govern diurnal variation in extracellular dopamine tone
Proceedings of the National Academy of Sciences - PNAS, v 111(26), pp E2751-E2759
01 Jul 2014
PMID: 24979798
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The majority of neurotransmitter systems shows variations in state-dependent cell firing rates that are mechanistically linked to variations in extracellular levels, or tone, of their respective neurotransmitter. Diurnal variation in dopamine tone has also been demonstrated within the striatum, but this neurotransmitter is unique, in that variation in dopamine tone is likely not related to dopamine cell firing; this is largely because of the observation that midbrain dopamine neurons do not display diurnal fluctuations in firing rates. Therefore, we conducted a systematic investigation of possible mechanisms for the variation in extracellular dopamine tone. Using microdialysis and fast-scan cyclic voltammetry in rats, as well as wild-type and dopamine transporter (DAT) knock-out mice, we demonstrate that dopamine uptake through the DAT and the magnitude of subsecond dopamine release is inversely related to the magnitude of extracellular dopamine tone. We investigated dopamine metabolism, uptake, release, D2 autoreceptor sensitivity, and tyrosine hydroxylase expression and activity as mechanisms for this variation. Using this approach, we have pinpointed the DAT as a critical governor of diurnal variation in extracellular dopamine tone and, as a consequence, influencing the magnitude of electrically stimulated dopamine release. Understanding diurnal variation in dopamine tone is critical for understanding and treating the multitude of psychiatric disorders that originate from perturbations of the dopamine system.
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Details
- Title
- Dopamine transporters govern diurnal variation in extracellular dopamine tone
- Creators
- Mark J Ferris - Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC 27157; andRodrigo A España - Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129Jason L Locke - Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC 27157; andJoanne K Konstantopoulos - Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC 27157; andJamie H Rose - Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC 27157; andRong Chen - Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC 27157; andSara R Jones - Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC 27157; and srjones@wakehealth.edu
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, v 111(26), pp E2751-E2759
- Publisher
- PNAS; United States
- Grant note
- P01 AA021099 / NIAAA NIH HHS F31 DA035558 / NIDA NIH HHS P50 DA006634 / NIDA NIH HHS T32 DA007246 / NIDA NIH HHS U01 AA014091 / NIAAA NIH HHS R01 DA021325 / NIDA NIH HHS R01 DA030161 / NIDA NIH HHS R01 DA014030 / NIDA NIH HHS K99 DA031791 / NIDA NIH HHS K01 DA025279 / NIDA NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000338118900018
- Scopus ID
- 2-s2.0-84903710971
- Other Identifier
- 991014878063704721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Neurosciences