Enhanced dopamine transporter function in striatum during nicotine withdrawal
Abstract
Spontaneous and antagonist-precipitated withdrawal from nicotine is characterized by marked deficits in extracellular dopamine (DA) in striatum, especially in nucleus accumbens, that have been thought to underlie the affective state associated with drug discontinuation. Uptake via the dopamine transporter (DAT) is a key mechanism for regulating the concentrations of extracellular DA. Accordingly, we questioned whether DAT expression and function are altered in striatum in nicotine withdrawal. Male mice, 30-35 g, were injected with nicotine free base 2 mg/kg, s.c., or saline four times daily for 14 days and euthanized 4-72 h after drug discontinuation. DA uptake into striatal synaptosomes was increased 12-24 h into nicotine withdrawal, and accompanied by elevated DAT mRNA in the substantia nigra pars compacta and ventral tegmental area, evaluated by in situ hybridization. The overflow of endogenous DA, measured under basal conditions in striatal slices ex vivo, was decreased during nicotine withdrawal in a time pattern paralleling to that of uptake. Added to striatal slices, the DAT inhibitor nomifensine reduced the observed difference in DA overflow between saline and nicotine withdrawn mice implying a role for the transporter. The presented data suggest that DAT is transiently upregulated in the striatum early during nicotine withdrawal, and enhanced transporter function contributes to the decreased extracellular DA levels.
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The hypodopaminergic state during withdrawal is produced by reduced DA release and increased DA re-uptake due to DAT upregulation.
“The hypodopaminergic state associated with withdrawal is produced by both a reduction in DA release and an increase in DA re-uptake [140]. Increased DA re-uptake is due to upregulation of the DA transporter (DAT) [137, 141].”
From Mechanistic insights into nicotine withdrawal (2011) · cites this paper as [141]
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- Authors
- Hadjiconstantinou, M., Duchemin, A., Zhang, H., & Neff, N. H.
- Affiliations
- The Ohio State University (US)
- Corresponding author
- Hadjiconstantinou, Maria
- ORCID
- Duchemin, Anne‐Marie
- Venue
- Synapse
- Publisher
- Wiley
- Published
- 2010-12-03
- Volume
- 65
- Issue
- 2
- Pages
- 91-98
- ISSN
- 0887-4476 (ISSN-L)
- 1098-2396
- OpenAlex
- W2041285633
- Cited by
- 20
- References
- 51
- Citations by year
- 2024: 1 · 2021: 1 · 2019: 1 · 2018: 1 · 2017: 2 · 2016: 2 · 2015: 3 · 2014: 1 · 2013: 3 · 2012: 1
- FWCI
- 1.03
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Synapse (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Keywords
- nicotine withdrawal, dopamine transporter, striatum, dopamine uptake, extracellular dopamine, nucleus accumbens, substantia nigra pars compacta, ventral tegmental area, nomifensine, synaptosomes
- MeSH terms
- Animals, Chromatography, High Pressure Liquid, Corpus Striatum, Disease Models, Animal, Dopamine, Drug Administration Schedule, Gene Expression Regulation, Male, Nicotine, RNA, Messenger, Substance Withdrawal Syndrome, Time Factors, Nicotinic Agonists, Dopamine Plasma Membrane Transport Proteins, Mice
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