Reinforcing effects of nicotine microinjections into the ventral tegmental area of mice: dependence on cholinergic nicotinic and dopaminergic D1 receptors
Abstract
We used an intracranial self-administration (ICSA) procedure to assess the involvement of the ventral tegmental area (VTA) nicotinic receptors in the rewarding effects of nicotine. We then challenged intra-VTA nicotine self-administration via systemic or local injections of dopamine (DA)-D1 and nicotinic receptor antagonists. C57BL/6J mice were stereotaxically implanted unilaterally with a guide cannula above the VTA. After 1 week of recovery, mice were allowed to discriminate between two arms of a Y-maze over seven daily sessions, one arm being reinforced by intracranial nicotine microinjection. Mice exhibited nicotine self-administration at both doses tested, i.e. 10 ng (21.6 pmol) and 100 ng (216 pmol)/50-nl injection. In contrast, mice receiving a 216-pmol nicotine dose 0.8 mm above VTA performed at chance level. Once the ICSA response was acquired, systemic pretreatment with the DA-D1 receptor antagonist SCH 23390 (25 microg/kg i.p.) or co-infusion of the nAChR antagonist DHbetaE with nicotine disrupted ICSA. Replacement of SCH 23390 by vehicle, or withdrawal of DHbetaE from nicotine/DHbetaE mixed solutions led to recovery of intra-VTA nicotine self-administration. We conclude that nicotinic receptors in the VTA, presumably alpha4beta2 nAChRs are critically to mediate the rewarding effects of nicotine and that DA-D1 receptors are also directly implicated.
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Mice learn to run on a Y-maze to self-administer nicotine into the VTA, an effect that can be diminished by systemic administration of dopamine antagonists.
“Mice learn to run on a Y-maze to self-administer nicotine into the VTA, an effect that can be diminished by systemic administration of dopamine antagonists”
From Dopamine reward circuitry: Two projection systems from the ventral midbrain to the nucleus accumbens–olfactory tubercle complex (2007) · cites this paper as David et al., 2006
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- Authors
- David, V., Besson, M., Changeux, J.-P., Granon, S., & Cazala, P.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Granon, Sylvie
- Venue
- Neuropharmacology
- Publisher
- Elsevier BV
- Published
- 2006-06
- Volume
- 50
- Issue
- 8
- Pages
- 1030-1040
- ISSN
- 0028-3908 (ISSN-L)
- OpenAlex
- W2139155720
- Cited by
- 87
- References
- 58
- Citations by year
- 2024: 1 · 2023: 1 · 2022: 1 · 2021: 5 · 2020: 2 · 2019: 3 · 2018: 1 · 2017: 2 · 2016: 1 · 2015: 4 · 2014: 6 · 2013: 6 · 2012: 8
- FWCI
- 4.32
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuropharmacology (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Institut Carnot Santé Animale
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Keywords
- nicotine, ventral tegmental area, nicotinic acetylcholine receptors, dopamine D1 receptor, nicotine self-administration, alpha4beta2 nAChR, SCH 23390, reward, cholinergic-dopaminergic interaction
- MeSH terms
- Animals, Behavior, Animal, Benzazepines, Dihydro-beta-Erythroidine, Dose-Response Relationship, Drug, Drug Combinations, Drug Interactions, Male, Mice, Inbred C57BL, Microinjections, Nicotine, Reaction Time, Receptors, Nicotinic, Reinforcement, Psychology, Self Administration, Spatial Behavior, Receptors, Dopamine D1, Ventral Tegmental Area, Dopamine Antagonists, Nicotinic Agonists, Nicotinic Antagonists, Maze Learning, Mice
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