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The motivational valence of nicotine in the rat ventral tegmental area is switched from rewarding to aversive following blockade of the α7-subunit-containing nicotinic acetylcholine receptor
Abstract
Rationale Within the mammalian ventral tegmental area (VTA), nicotine produces both aversive and rewarding motivational effects. However, the specific neuronal nicotinic acetylcholine receptor (nAChR) subtypes responsible for these effects are not clearly understood. Objectives In the present study, we challenged the motivational effects of nicotine directly in the VTA with nAChR subunit specific antagonists. Methods Using an unbiased place-conditioning procedure as a behavioural assay, we performed bilateral microinfusions of nicotine over a wide range of concentrations (0.008, 8, 24 and 48 nmol/0.5 microl) and challenged the aversive and reinforcing behavioural effects of these nicotine doses with co-administration of di-hydro-beta-erythroidine (DHbetaE) (5 or 50 nmol/0.5 microl), a nAChR antagonist with higher relative affinity for the alpha4beta2 nAChR subunit, methyllycaconitine citrate (MLA) (0.4 or 4 nmol/0.5 microl), a nAChR antagonist that displays greater relative affinity for the alpha7 nAChR, and the NMDA receptor antagonist, d-2-amino-7-phosphoheptanoic acid (AP-7; 18 nmol/0.5 microl). Results The alpha4beta2 antagonist DHbetaE blocked both the rewarding and aversive properties of intra-VTA nicotine. However, the alpha7 antagonist MLA blocked nicotine reward and switched the motivational valence of higher doses of nicotine (8-48 nmol/0.5 microl) from rewarding to aversive. The NMDA antagonist AP-7 blocked both the aversive and rewarding effects of intra-VTA nicot…
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“An accumulation of data suggests that both the β2* and α7 nAChR subtypes contribute to nicotine-associated increases in DA release and associated nicotine-dependent behaviors (Corrigall et al., 1994; Epping-Jordan et al., 1999; Laviolette and van der Kooy, 2003; Mansvelder et al., 2002; Picciotto et al., 1998; Pidoplichko et al., 2004; Shoaib and Stolerman, 1994).”
From It is not “either/or”: Activation and desensitization of nicotinic acetylcholine receptors both contribute to behaviors related to nicotine addiction and mood (2008) · cites this paper as Laviolette and van der Kooy, 2003
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Tzschentke, T. M. (2007) · Addiction Biology · doi:10.1111/j.1369-1600.2007.00070.x · Cited by 1,336
Guidelines on nicotine dose selection for in vivo research
Matta, S. G., Balfour, D. J., Benowitz, N. L., Boyd, R. T., Buccafusco, J. J., Caggiula, A. R., Craig, C. R., Collins, A. C., Damaj, M. I., Donny, E. C., et al. (2007) · Psychopharmacology · doi:10.1007/s00213-006-0441-0 · Cited by 824
Nicotine Activation of α4* Receptors: Sufficient for Reward, Tolerance, and Sensitization
Tapper, A. R., McKinney, S. L., Nashmi, R., Schwarz, J., Deshpande, P., Labarca, C., Whiteaker, P., Marks, M. J., Collins, A. C., & Lester, H. A. (2004) · Science · doi:10.1126/science.1099420 · Cited by 686
The neurobiology of positive emotions
Burgdorf, J., & Panksepp, J. (2006) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2005.06.001 · Cited by 677
The neurobiology of nicotine addiction: bridging the gap from molecules to behaviour
Laviolette, S. R., & van der Kooy, D. (2004) · Nature reviews. Neuroscience · doi:10.1038/nrn1298 · Cited by 469
Self-citation
Metadata
- Authors
- Laviolette, S. R., & van der Kooy, D.
- Affiliations
- University of Toronto (CA)
- Venue
- Psychopharmacology
- Published
- 2003-02-05
- Volume
- 166
- Issue
- 3
- Pages
- 306-313
- ISSN
- 0033-3158 (ISSN-L)
- OpenAlex
- W1540199296
- Cited by
- 113
- References
- 30
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 1 · 2022: 6 · 2021: 3 · 2020: 2 · 2018: 4 · 2017: 4 · 2016: 2 · 2015: 4 · 2014: 8 · 2013: 8 · 2012: 5
- FWCI
- 2.29
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- 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 › Public Health, Environmental and Occupational Health › Smoking Behavior and Cessation
- Keywords
- nicotine, ventral tegmental area, nicotinic acetylcholine receptors, alpha7 nAChR, alpha4beta2 nAChR, nicotine reward, nicotine aversion, dihydro-beta-erythroidine, methyllycaconitine, NMDA receptor, glutamatergic mechanisms, place conditioning, microinfusion
- MeSH terms
- Aconitine, Animals, Conditioning, Operant, Dihydro-beta-Erythroidine, Dose-Response Relationship, Drug, Male, Microinjections, Motivation, Nicotine, Receptors, Nicotinic, Reinforcement, Psychology, Reward, 2-Amino-5-phosphonovalerate, Receptors, N-Methyl-D-Aspartate, Rats, Wistar, Ventral Tegmental Area, Excitatory Amino Acid Antagonists, Nicotinic Agonists, Nicotinic Antagonists, Rats, alpha7 Nicotinic Acetylcholine Receptor
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