title: Dopamine transporters govern diurnal variation in extracellular dopamine tone.
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.
authors: Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC 27157; and.
authors: Mark J
authors: MJ
authors: Ferris
authors: Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129.
authors: Rodrigo A
authors: RA
authors: España
authors: Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC 27157; and.
authors: Jason L
authors: JL
authors: Locke
authors: Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC 27157; and.
authors: Joanne K
authors: JK
authors: Konstantopoulos
authors: Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC 27157; and.
authors: Jamie H
authors: JH
authors: Rose
authors: Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC 27157; and.
authors: Rong
authors: R
authors: Chen
authors: Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC 27157; and srjones@wakehealth.edu.
authors: Sara R
authors: SR
authors: Jones
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002851:Chromatography, High Pressure Liquid; D002940:Circadian Rhythm / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D017551:Microdialysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine
keywords: caudate-putamen; circadian; nucleus accumbens