Illicit dopamine transients: reconciling actions of abused drugs
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Phasic increases in brain dopamine are required for cue-directed reward seeking. While compelling within the framework of appetitive behavior, the view that illicit drugs hijack reward circuits by hyper-activating these dopamine transients is inconsistent with established psychostimulant pharmacology. However, recent work reclassifying amphetamine (AMPH), cocaine, and other addictive dopamine-transporter inhibitors (DAT-Is) supports transient hyper-activation as a unifying hypothesis of abused drugs. We argue here that reclassification also identifies generating burst firing by dopamine neurons as a keystone action. Unlike natural rewards, which are processed by sensory systems, drugs act directly on the brain. Consequently, to mimic natural reward and exploit reward circuits, dopamine transients must be elicited de novo. Of available drug targets, only burst firing achieves this essential outcome.
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Drugs mimic the dopamine increases produced by phasic dopamine firing associated with rewarding stimuli.
“In this respect, drugs emulate the increases in dopamine triggered by phasic dopamine firing, which are the firing frequencies of dopamine neurons associated with rewarding stimuli.”
From Neurobiology of addiction: a neurocircuitry analysis (2016) · cites this paper as [42]
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Self-citation
- Authors
- Covey, D. P., Roitman, M. F., & Garris, P. A.
- Affiliations
- Illinois State University (US)
- University of Illinois Chicago (US)
- Corresponding author
- Garris, Paul A.
- Venue
- Trends in Neurosciences
- Publisher
- Elsevier BV
- Published
- 2014-04
- Volume
- 37
- Issue
- 4
- Pages
- 200-210
- ISSN
- 0166-2236 (ISSN-L)
- PMC
- PMC4064368
- OpenAlex
- W1988355411
- Semantic Scholar
- dc5379d7e5643f1ccfd2724811dcbb5c4b5d3a84
- Cited by
- 90
- References
- 130
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 6 · 2023: 7 · 2022: 7 · 2021: 5 · 2020: 5 · 2019: 9 · 2018: 6 · 2017: 10 · 2016: 16 · 2015: 10 · 2014: 4
- FWCI
- 1.50
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Trends in Neurosciences (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Science Foundation
- National Institute on Drug Abuse (DA 024036, R03DA021770, DA025634, R01DA024036, R01DA025634, DA021770)
- 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
- illicit drug abuse, psychostimulants, dopaminergic neurons, burst firing, dopamine transporter inhibitors, amphetamine, cocaine, reward systems, drug reclassification
- MeSH terms
- Animals, Brain, Dopamine, Humans, Models, Neurological, Illicit Drugs, Substance-Related Disorders, Dopamine Plasma Membrane Transport Proteins, Dopaminergic Neurons
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