Metabotropic Glutamate 2/3 Receptors in the Ventral Tegmental Area and the Nucleus Accumbens Shell Are Involved in Behaviors Relating to Nicotine Dependence
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The motivation to maintain nicotine self-administration and dependence may involve alterations in glutamatergic neurotransmission. Metabotropic glutamate (mGlu) 2/3 receptors regulate glutamate and dopamine release in the ventral tegmental area (VTA) and the nucleus accumbens (NAc) shell, two brain areas critically involved in reward and motivational processes. We found that acute systemic, as well as intra-VTA or intra-NAc, administration of the mGlu2/3 receptor agonist LY379268 [(−)-2-oxa-4-aminobicyclo[3.1.0]hexane-4,6-dicarboxylate] decreased nicotine, but not food, self-administration in rats. In addition, nicotine self-administration downregulated mGlu2/3 receptor function in corticolimbic rat brain sites including the VTA and the NAc, demonstrated by decreased coupling of mGlu2/3 receptors to G-proteins in the [ 35 S]GTPγS binding assay. Furthermore, repeated treatment with LY379268 reduced nicotine self-administration at the beginning of a 14 d treatment period; however, the number of nicotine infusions earned gradually returned to baseline levels, indicating tolerance to the effects of repeated LY379268 treatment. Finally, LY379268 administration decreased both cue-induced reinstatement of nicotine- and food-seeking behavior. Together, these findings indicate an important role for mGlu2/3 receptors in the posterior VTA and the NAc shell in the mediation of the rewarding effects of nicotine and potentially in cue-induced nicotine-seeking behavior.
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Activation of mGlu2/3 receptors decreases nicotine self-administration.
“activation of mGlu2/3 receptors decreases nicotine self-administration (Liechti et al. 2007)”
From Short- and Long-Term Consequences of Nicotine Exposure during Adolescence for Prefrontal Cortex Neuronal Network Function (2012) · cites this paper as Liechti et al. 2007
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- Authors
- Liechti, M. E., Lhuillier, L., Kaupmann, K., & Markou, A.
- Affiliations
- University of California San Diego (US)
- Novartis (Switzerland) (CH)
- Corresponding author
- Markou, Athina
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2007-08-22
- Volume
- 27
- Issue
- 34
- Pages
- 9077-9085
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6672208
- OpenAlex
- W1996790468
- Cited by
- 193
- References
- 2
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 2 · 2023: 10 · 2022: 7 · 2021: 4 · 2020: 7 · 2019: 7 · 2018: 8 · 2017: 13 · 2016: 10 · 2015: 20 · 2014: 17 · 2013: 10 · 2012: 16
- FWCI
- 5.44
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Science Foundation
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (108501)
- National Institute on Drug Abuse (DA 11946, R56DA011946, R01DA011946)
- 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
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- nicotine dependence, nicotine self-administration, ventral tegmental area, nucleus accumbens shell, LY379268, G protein coupling, receptor down-regulation, tolerance (pharmacology and immunology), cue-induced reinstatement, food-seeking behavior, glutamatergic neurotransmission, dopamine release, reward
- MeSH terms
- Amino Acids, Analysis of Variance, Animals, Behavior, Animal, Cues, Dose-Response Relationship, Drug, Drug Interactions, Food Preferences, Male, Nicotine, Nucleus Accumbens, Protein Binding, Reinforcement, Psychology, Self Administration, Tobacco Use Disorder, Guanosine 5'-O-(3-Thiotriphosphate), Rats, Wistar, Ventral Tegmental Area, Receptors, Metabotropic Glutamate, Excitatory Amino Acid Agonists, Bridged Bicyclo Compounds, Heterocyclic, Rats
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