The mesolimbic dopaminergic system is implicated in the reinforcing effects of nicotine
Abstract
Rats were trained to self-administer nicotine on a fixed-ratio schedule of reinforcement. Infusion of the nicotinic antagonist chlorisondamine into the cerebral ventricles produced a sustained reduction in nicotine self-administration compared to vehicle-treated controls. Lesions of the mesolimbic dopamine system were produced by microinfusion of 6-hydroxydopamine into the nucleus accumbens. Following production of the lesions, nicotine self-administration was markedly reduced for the 3-week test period; motor impairment did not appear to be responsible. Post mortem analysis of brain tissue showed that the lesion produced a pronounced decrease in dopamine content of the nucleus accumbens and the olfactory tubercle, and a small depletion in the striatum. These data demonstrate that the reinforcing effects of nicotine occur within the central nervous system, and that the mesolimbic dopamine projection plays an important role in these effects.
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Lesions of the VTA and its primary projection area, the NAc, greatly attenuate nicotine self-administration and the psychostimulant properties of nicotine.
“Lesions of the ventral tegmental area (VTA) and its primary projection area, the nucleus accumbens (NAc), greatly attenuate nicotine self-administration and the psychostimulant properties of nicotine”
From Mechanisms of Nicotine Addiction (2021) · cites this paper as Corrigall et al. 1992
Lesion or inactivation of the mesolimbic DA system in the VTA or NAc decreases cocaine, amphetamine, heroin, and nicotine self-administration in rats.
“In addition, lesion or inactivation of the mesolimbic DA system in the VTA [137,138] or in the NAc [139-143] decreases cocaine, amphetamine, heroin, and nicotine self-administration in rats.”
From Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings (2012) · cites this paper as [139]
Drugs that selectively inhibit α4β2* and/or α6β2* nAChRs block behaviors linked to nicotine reward and reinforcement when infused or given systemically.
“In addition, infusion and systemic administration of drugs that selectively inhibit ␣42* and/or ␣62* nAChRs blocked behaviors linked to nicotine reward and reinforcement”
From Varenicline Is a Potent Partial Agonist at α6β2* Nicotinic Acetylcholine Receptors in Rat and Monkey Striatum (2012) · cites this paper as Corrigall et al., 1992
The VTA at least partly mediates the rewarding effects of nicotine, opiates, cannabinoids and ethanol.
“The VTA at least partly mediates the rewarding effects of nicotine, opiates, cannabinoids and ethanol.”
From Dopamine reward circuitry: Two projection systems from the ventral midbrain to the nucleus accumbens–olfactory tubercle complex (2007) · cites this paper as Corrigall et al., 1992
Intravenous self-administration of nicotine in rats is attenuated by selective lesions to VTA dopamine neurons projecting to the ventral striatum.
“Intravenous self-administration of nicotine in rats is attenuated by selective lesions to VTA dopamine neurons projecting to the ventral striatum”
From Dopamine reward circuitry: Two projection systems from the ventral midbrain to the nucleus accumbens–olfactory tubercle complex (2007) · cites this paper as Corrigall et al., 1992
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- Authors
- Corrigall, W. A., Franklin, K. B. J., Coen, K. M., & Clarke, P. B. S.
- Affiliations
- McGill University (CA)
- ORCID
- Clarke, Paul B. S.
- Venue
- Psychopharmacology
- Published
- 1992-06
- Volume
- 107
- Issue
- 2-3
- Pages
- 285-289
- ISSN
- 0033-3158 (ISSN-L)
- 1432-2072
- OpenAlex
- W2011246896
- Cited by
- 829
- References
- 40
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 5 · 2023: 9 · 2022: 10 · 2021: 8 · 2020: 37 · 2019: 11 · 2018: 19 · 2017: 11 · 2016: 16 · 2015: 24 · 2014: 39 · 2013: 32 · 2012: 30
- FWCI
- 5.30
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01da005970-02)
- National Institute on Drug Abuse (DA 05970)
- 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, mesolimbic dopamine system, nicotine self-administration, nicotine reinforcement, nucleus accumbens, 6-hydroxydopamine lesion, chlorisondamine, dopamine depletion, olfactory tubercle, striatum, fixed-ratio schedules
- MeSH terms
- Animals, Brain Chemistry, Chlorisondamine, Conditioning, Operant, Dopamine, Limbic System, Male, Nicotine, Reinforcement, Psychology, Reinforcement Schedule, Self Administration, Stereotaxic Techniques, Oxidopamine, Rats
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