Journal article
Dopamine transporter function fluctuates across sleep/wake state: potential impact for addiction
Neuropsychopharmacology (New York, N.Y.), v 46(4), pp 699-708
01 Mar 2021
PMID: 33032296
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The dopamine transporter (DAT) has been implicated in a variety of arousal-related processes including the regulation of motor activity, learning, motivated behavior, psychostimulant abuse, and, more recently, sleep/wake state. We previously demonstrated that DAT uptake regulates fluctuations in extracellular dopamine (DA) in the striatum across the light/dark cycle with DA levels at their highest during the dark phase and lowest during the light phase. Despite this evidence, whether fluctuations in DA uptake across the light/dark cycle are associated with changes in sleep/wake has not been tested. To address this, we employed a combination of sleep/wake recordings, fast scan cyclic voltammetry, and western blotting to examine whether sleep/wake state and/or light/dark phase impact DA terminal neurotransmission in male rats. Further, we assessed whether variations in plasma membrane DAT levels and/or phosphorylation of the threonine 53 site on the DAT accounts for fluctuations in DA neurotransmission. Given the extensive evidence indicating that psychostimulants increase DA through interactions with the DAT, we also examined to what degree the effects of cocaine at inhibiting the DAT vary across sleep/wake state. Results demonstrated a significant association between individual sleep/wake states and DA terminal neurotransmission, with higher DA uptake rate, increased phosphorylation of the DAT, and enhanced cocaine potency observed after periods of sleep. These findings suggest that sleep/wake state influences DA neurotransmission in a manner that is likely to impact a host of DA-dependent processes including a variety of neuropsychiatric disorders.
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Details
- Title
- Dopamine transporter function fluctuates across sleep/wake state: potential impact for addiction
- Creators
- I. P. Alonso - Drexel UniversityJ. A. Pino - University of AtacamaS. Kortagere - Drexel UniversityG. E. Torres - City College of New YorkR. A. Espana - Drexel University
- Publication Details
- Neuropsychopharmacology (New York, N.Y.), v 46(4), pp 699-708
- Publisher
- Springer Nature
- Number of pages
- 10
- Grant note
- DA031900; MH106912; DA038598 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA 11191049 / Fondecyt Initiation Fund
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology; Neurobiology and Anatomy
- Web of Science ID
- WOS:000580712400001
- Scopus ID
- 2-s2.0-85092156101
- Other Identifier
- 991019167817204721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Neurosciences
- Pharmacology & Pharmacy
- Psychiatry