Vesicular glutamate transporter 2 expression in the ventral tegmental area of outbred male rats following exposure to nicotine and alcohol
Open accessAbstract
Initiation of use/co-use of nicotine and alcohol, commonly occuring in an episodic manner during adolescence, can imprint vulnerability to the developing brain and lead to addiction. The ventral tegmental area (VTA) is a key heterogenous region of the mesocorticolimbic circuit involved in the binge-drinking and intoxication step of the addiction circuit. Higher human post-mortem VTA expression of Vesicular Glutamate Transporter 2 (VGLUT2), a marker of the glutamatergic phenotype also expressed in dopaminergic [Tyrosine Hydroxylase (Th)-positive] neurons, has been associated with chronic nicotine use and co-use with alcohol. The present study aimed to map and characterize the Vglut2- and Th-expressing neurons in the VTA of adolescent male rats exposed or not to prolonged (six-weeks) episodic (three consequtive days/week) nicotine and/or alcohol administration. Nicotine (0.35 mg/kg free base) was injected subcutaneously, whereas alcohol (2 g/kg 20%) was administrated via gavage. Vglut2 and Th mRNA was assessed in the anterior and posterior VTA by use of in situ hybridization. The profile of neurons varied with substance-exposure among VTA subregions. Th-only expressing neurons were more abundant in the posterior VTA of the group exposed to nicotine-only, compared to controls. The same neurons were, on the contrary, less present in the anterior VTA of animals exposed to alcohol-only, who also displayed a higher number of Vglut2-expressing neurons in the lateral anterior VTA. VTA Vglut2- and Th-only neurons seem differentially involved in the effects of adolescent episodic nicotine and alcohol exposure in the anterior and posterior VTA.
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Nicotine in adolescence increases the proportion of DA neurons that do not express the vesicular glutamate transporter (TH+Vglut- neurons) in the posterior VTA in rats.
“Structural analysis of VTA neuron populations note that nicotine in adolescence increased the proportion of DA neurons that do not express the vesicular glutamate transporter (TH+Vglut- neurons) in the posterior VTA in rats [142].”
From Adolescent nicotine exposure and persistent neurocircuitry changes: unveiling lifelong psychiatric risks (2025) · cites this paper as [142]
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- Authors
- Vrettou, M., Thalhammer, S. B., Svensson, A.-L., Dumas, S., Nilsson, K. W., Wallén-Mackenzie, Å., Fredriksson, R., Nylander, I., & Comasco, E.
- Affiliations
- Uppsala University (SE)
- Corresponding author
- Comasco, Erika
- Venue
- Drug and Alcohol Dependence Reports
- Publisher
- Elsevier BV
- Published
- 2023-09
- Volume
- 8
- Pages
- 100180
- ISSN
- 2772-7246 (ISSN-L)
- PMC
- PMC10391930
- OpenAlex
- W4384207004
- Cited by
- 4
- References
- 60
- Citations by year
- 2025: 2 · 2024: 1 · 2023: 1
- FWCI
- 0.48
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Drug and Alcohol Dependence Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- KTH Publication Database DiVA (KTH Royal Institute of Technology) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Keywords
- vesicular glutamate transporter 2, ventral tegmental area, nicotine, alcohol, tyrosine hydroxylase, dopaminergic neurons, glutamatergic neurons, addiction vulnerability, mesocorticolimbic circuit
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