The mesolimbic dopamine system: The final common pathway for the reinforcing effect of drugs of abuse?
Abstract
In this review we will critically assess the hypothesis that the reinforcing effect of virtually all drugs of abuse is primarily dependent on activation of the mesolimbic dopamine system. The focus is on five classes of abused drugs: psychostimulants, opiates, ethanol, cannabinoids and nicotine. For each of these drug classes, the pharmacological and physiological mechanisms underlying the direct or indirect influence on mesolimbic dopamine transmission will be reviewed. Next, we evaluate behavioral pharmacological experiments that specifically assess the influence of activation of the mesolimbic dopamine system on drug reinforcement, with particular emphasis on animal experiments using drug self-administration paradigms. There is overwhelming evidence that all five classes of abused drugs increase dopamine transmission in limbic regions of the brain through interactions with a variety of transporters, ionotropic receptors and metabotropic receptors. Behavioral pharmacological experiments indicate that increased dopamine transmission is clearly both necessary and sufficient to promote psychostimulant reinforcement. For the other four classes of abused substances, self-administration experiments suggest that although increasing mesolimbic dopamine transmission plays an important role in the reinforcing effects of opiates, ethanol, cannabinoids and nicotine, there are also dopamine-independent processes that contribute significantly to the reinforcing effects of these compounds…
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The mesolimbic dopaminergic pathway is associated with addictive behaviors, including drug use and binge eating disorders.
“The mesolimbic dopaminergic pathway has been associated with addictive behaviors, including drug use and binge eating disorders [7, 8].”
From The Impact of Social Media & Technology on Child and Adolescent Mental Health (2025) · cites this paper as [7]
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“It has to be noted that the mesocorticolimbic dopaminergic pathway has been suggested as a common final pathway in drug reinforcement (Pierce & Kumaresan, 2006) and also dependence to AMP or cocaine is influenced by anxious‐impulsive personality traits (Ersche et al., 2012).”
Background
- Authors
- Pierce, R. C., & Kumaresan, V.
- Affiliations
- Boston University (US)
- Corresponding author
- Pierce, R. Christopher
- Venue
- Neuroscience & Biobehavioral Reviews
- Publisher
- Elsevier BV
- Published
- 2006-01
- Volume
- 30
- Issue
- 2
- Pages
- 215-238
- ISSN
- 0149-7634 (ISSN-L)
- OpenAlex
- W1998674360
- Cited by
- 913
- References
- 24
- Citations by year
- 2026: 22 · 2025: 24 · 2024: 14 · 2023: 24 · 2022: 44 · 2021: 30 · 2020: 100 · 2019: 38 · 2018: 41 · 2017: 37 · 2016: 65 · 2015: 64 · 2014: 58 · 2013: 54 · 2012: 53
- FWCI
- 2.39
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience & Biobehavioral Reviews (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Brown University
- National Institute on Drug Abuse (R01DA015214)
- National Center for Research Resources (P20 RR1578)
- 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
- mesolimbic dopamine system, drug reinforcement, self-administration, psychostimulants, opiates, ethanol, cannabinoids, nicotine, dopamine transporter, ligand-gated ion channels, metabotropic receptors, addiction
- MeSH terms
- Ethanol, Central Nervous System Stimulants, Animals, Cannabinoids, Dopamine, Humans, Limbic System, Narcotics, Neural Pathways, Nicotine, Receptors, Dopamine, Reinforcement, Psychology, Mice, Knockout, Substance-Related Disorders, Dopamine Plasma Membrane Transport Proteins, Mice
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