Synaptic plasticity and addiction: Learning mechanisms gone awry
Open accessAbstract
Experience-dependent changes in synaptic strength, or synaptic plasticity, may underlie many learning processes. In the reward circuit for example, synaptic plasticity may serve as a cellular substrate for goal-directed behaviors. Addictive drugs, through a surge of dopamine released from neurons of the ventral tegmental area, induce widespread synaptic adaptations within this neuronal circuit. Such drug-evoked synaptic plasticity may constitute an early cellular mechanism eventually causing compulsive drug-seeking behavior in some drug users. In the present review we will discuss how different classes of addictive drugs cause an increase of dopamine release and describe their effects on synapses within the mesolimbic dopamine system. We will emphasize the early synaptic changes in the ventral tegmental area common to all additive drugs and go on to show how these adaptations may reorganize neuronal circuits, eventually leading to behaviors that define addiction.
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The rules for subsequent activity-dependent plasticity are inverted after a dose of an addictive drug.
“As a consequence, the rules for subsequent activity-dependent plasticity are inverted (Mameli and Lu ¨scher 2011).”
From NMDA receptor-dependent long-term potentiation and long-term depression (LTP/LTD). (2012) · cites this paper as Mameli and Lüscher 2011
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Wise, R. A. (2004) · Nature Reviews Neuroscience · doi:10.1038/nrn1406 · Cited by 3,379 · cited 1× · see citing works
“Together, the VTA, the NAc and the PFC constitute the motivational circuit of which the crucial role in motivated behaviors and reward learning has been extensively reviewed (Berke and Hyman, 2000; Wise, 2004; Berridge, 2007).”
BackgroundSwanson, L. W. (1982) · Brain Research Bulletin · doi:10.1016/0361-9230(82)90145-9 · Cited by 1,718 · see citing works
Nicotine reinforcement and cognition restored by targeted expression of nicotinic receptors
Maskos, U., Molles, B. E., Pons, S., Besson, M., Guiard, B. P., Guilloux, J.-P., Evrard, A., Cazala, P., Cormier, A., Mameli-Engvall, M., et al. (2005) · Nature · doi:10.1038/nature03694 · Cited by 566 · see citing works
Bellone, C., & Lüscher, C. (2006) · Nature Neuroscience · doi:10.1038/nn1682 · Cited by 429 · see citing works
Self-citationNeural bases for addictive properties of benzodiazepines
Tan, K. R., Brown, M., Labouèbe, G., Yvon, C., Creton, C., Fritschy, J.-M., Rudolph, U., & Lüscher, C. (2010) · Nature · doi:10.1038/nature08758 · Cited by 397 · see citing works
Self-citationPrefrontal cortex AMPA receptor plasticity is crucial for cue-induced relapse to heroin-seeking
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NMDA receptor-dependent long-term potentiation and long-term depression (LTP/LTD).
Luscher, C., & Malenka, R. C. (2012) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a005710 · Cited by 1,110 · see citing works
Self-citationManipulating a “Cocaine Engram” in Mice
Hsiang, H.-L. (., Epp, J. R., van den Oever, M. C., Yan, C., Rashid, A. J., Insel, N., Ye, L., Niibori, Y., Deisseroth, K., Frankland, P. W., et al. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.3327-14.2014 · Cited by 131 · see citing works
- Authors
- Mameli, M., & Lüscher, C.
- Affiliations
- Inserm (FR)
- University of Geneva (CH)
- Corresponding author
- Mameli, Manuel
- Lüscher, Christian
- Venue
- Neuropharmacology
- Publisher
- Elsevier BV
- Published
- 2011-12
- Volume
- 61
- Issue
- 7
- Pages
- 1052-1059
- ISSN
- 0028-3908 (ISSN-L)
- OpenAlex
- W2015707766
- Cited by
- 96
- References
- 6
- Citations by year
- 2026: 4 · 2025: 1 · 2024: 6 · 2023: 5 · 2022: 4 · 2021: 4 · 2020: 3 · 2019: 4 · 2018: 10 · 2017: 7 · 2016: 11 · 2015: 6 · 2014: 10 · 2013: 12 · 2012: 8
- FWCI
- 0.94
- Type
- journal article
- Language
- en
- Open access
- Licence
- Locations
- Neuropharmacology (publishedVersion)
- PubMed (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Funders
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- 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 › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- synaptic plasticity, addiction, dopamine release, ventral tegmental area, mesolimbic dopamine system, reward systems, drug-seeking behavior, synaptic adaptation, goal-directed behavior, learning mechanisms
- MeSH terms
- Animals, Cocaine, Dopamine, Humans, Learning, Neuronal Plasticity, Neurons, Ventral Tegmental Area, Dopamine Uptake Inhibitors, Substance-Related Disorders, Cocaine-Related Disorders, Drug-Seeking Behavior
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