Increased expression of VMAT2 in dopaminergic neurons during nicotine withdrawal
Abstract
Evidence suggests that the vesicular monoamine transporter-2 (VMAT2) is regulated in striatum and dopamine (DA) may play a role in its regulation. DA is an important mediator of the behavioral actions of nicotine, and dopaminergic neurotransmission is altered following nicotine administration. We investigated the effect of nicotine withdrawal on the expression of VMAT2 in the midbrain DA neurons in animals dependent to nicotine. Mice were injected with nicotine free base 2mg/kg, sc, four times daily for 14 days and killed 12-72h after drug discontinuation. VMAT2 protein was increased in the striatum of nicotine-treated mice in a time-dependent fashion at all times studied. Furthermore, in situ hybridization studies demonstrated that VMAT2 mRNA was elevated in the substantia nigra pars compacta and ventral tegmental area, indicating enhanced gene expression and subsequent protein synthesis. Tissue DA content and synthesis were unaltered in the striatum of nicotine-treated mice at the times studied. However, basal DA release was decreased at 12 and 24h after nicotine discontinuation which coincided with the elevated levels of VMAT2 protein. VMAT2 up-regulation might be a compensatory mechanism to restore and maintain synaptic transmission in dopaminergic midbrain neurons during nicotine withdrawal.
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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 [140]
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References 40 · Cited by 18
- Authors
- Duchemin, A.-M., Zhang, H., Neff, N. H., & Hadjiconstantinou, M.
- Affiliations
- The Ohio State University (US)
- Corresponding author
- Hadjiconstantinou, Maria
- ORCID
- Duchemin, Anne-Marie
- Venue
- Neuroscience Letters
- Publisher
- Elsevier BV
- Published
- 2009-12
- Volume
- 467
- Issue
- 2
- Pages
- 182-186
- ISSN
- 0304-3940 (ISSN-L)
- OpenAlex
- W2073114493
- Cited by
- 18
- References
- 40
- Citations by year
- 2024: 1 · 2019: 1 · 2018: 1 · 2016: 2 · 2015: 1 · 2014: 3 · 2012: 1
- FWCI
- 1.24
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience Letters (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Keywords
- vesicular monoamine transporter 2, nicotine withdrawal, dopaminergic neurons, dopamine release, substantia nigra pars compacta, ventral tegmental area, striatum, nicotine dependence, midbrain dopamine
- MeSH terms
- Animals, Corpus Striatum, Dopamine, Male, Neurons, Nicotine, RNA, Messenger, Substance Withdrawal Syndrome, Substantia Nigra, Biomarkers, Ventral Tegmental Area, Vesicular Monoamine Transport Proteins, Mice
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