Phasic Dopamine Signaling During Behavior, Reward, and Disease States
Abstract
The neurotransmitter dopamine is important in reward processing, however its precise modulatory role is still being investigated. Carbon-fiber microelectrodes can be used to monitor dopamine on a subsecond time scale in the striatum and nucleus accumbens of rats during behavior, and this approach is providing new insights into the mechanisms that control its extracellular concentration as well as the conditions under which it is released. Three main processes govern the amount of dopamine measured extrasynaptically: exocytotic release, neuronal uptake, and diffusion away from the release site. By monitoring local extracellular dopamine concentrations in the striatum following electrical stimulation of dopamine-containing neurons, release, uptake and diffusion can be individually examined and quantified. Dopaminergic neurons have been shown to fire in two firing modes, tonic and bursts at higher frequency. Electrical stimulation can be designed to mimic either mode to examine their effects on dopamine release. Burst firing causes a transient increase in extracellular dopamine while tonic firing causes a new steady-state level. In behaving primates, dopaminergic neurons display short-latency, phasic firing to primary reward and conditioned cues associated with reward. These bursts code differences between actual and predicted rewards. In rats, transient dopamine release in terminal regions that mimics that seen during burst firing has been demonstrated during reward-related cues. Taken together, these studies indicate that phasic dopamine release is a critical mediator of reward-related processes.
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These conduction delays lead to prediction errors that cause certain psychotic symptoms directly and ultimately underpin the excessive phasic dopamine neurotransmission associated with psychotic symptoms of schizophrenia.
“These conduction delays lead to prediction errors which, in addition to causing certain psychotic symptoms directly, ultimately also underpin the excessive phasic dopamine neurotransmission that has been associated with the psychotic symptoms of schizophrenia.6,7”
From Schizophrenia, myelination, and delayed corollary discharges: a hypothesis (2012) · cites this paper as [6]
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- Authors
- Wightman, R., & Heien, M.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Venue
- CNS & Neurological Disorders - Drug Targets
- Publisher
- Bentham Science Publishers Ltd.
- Published
- 2006-02-01
- Volume
- 5
- Issue
- 1
- Pages
- 99-108
- ISSN
- 1568-007X (ISSN-L)
- 1871-5273
- OpenAlex
- W2009699988
- Cited by
- 68
- References
- 0
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 5 · 2019: 1 · 2018: 3 · 2017: 2 · 2016: 2 · 2015: 3 · 2014: 3 · 2013: 3 · 2012: 7
- FWCI
- 2.91
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- CNS & Neurological Disorders - Drug Targets (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute on Drug Abuse (DA10900, R01DA010900)
- 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
- dopamine signaling, phasic dopamine release, reward processing, striatum, nucleus accumbens, carbon fiber microelectrodes, extracellular dopamine, dopamine uptake, burst firing, tonic firing, electrical stimulation
- MeSH terms
- Action Potentials, Animals, Cues, Dopamine, Humans, Synaptic Transmission, Neurons, Nucleus Accumbens, Psychotropic Drugs, Reward
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