Cannabinoids Enhance Subsecond Dopamine Release in the Nucleus Accumbens of Awake Rats
Open accessAbstract
Dopaminergic neurotransmission has been highly implicated in the reinforcing properties of many substances of abuse, including marijuana. Cannabinoids activate ventral tegmental area dopaminergic neurons, the main ascending projections of the mesocorticolimbic dopamine system, and change their spiking pattern by increasing the number of impulses in a burst and elevating the frequency of bursts. Although they also increase time-averaged striatal dopamine levels for extended periods of time, little is known about the temporal structure of this change. To elucidate this, fast-scan cyclic voltammetry was used to monitor extracellular dopamine in the nucleus accumbens of freely moving rats with subsecond timescale resolution. Intravenous administration of the central cannabinoid (CB 1) receptor agonist,R(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-(1-naphthalenyl) methanone mesylate, dose-dependently produced catalepsy, decreased locomotion, and reduced the amplitude of electrically evoked dopamine release while markedly increasing the frequency of detected (nonstimulated) dopamine concentration transients. The CB 1 receptor antagonist [N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methylpyrazole-3-carboxamide] reversed and prevented all agonist-induced effects but did not show effects on dopamine release when injected alone. These data demonstrate that doses of a cannabinoid agonist known to increase burst firing produce ongoing fluctuations in extracellular dopamine on a previously unrecognized temporal scale in the nucleus accumbens.
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Fast-scanning cyclic voltammetry studies have shown an increased frequency of spontaneous phasic DA signals in the NAc in response to cannabinoids and nicotine in awake, behaving animals, and temporally distinct DA signals in response to cocaine.
“In addition, studies using fast-scanning cyclic voltammetry, which can detect the level of DA release in the intact brain on a timescale of seconds, have shown an increased frequency of spontaneous phasic DA signals in the NAc in response to cannabinoids and nicotine in awake, behaving animals [125,126], and also temporally distinct DA signals in response to cocaine [127].”
From Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings (2012) · cites this paper as [125]
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- Authors
- Cheer, J. F., Wassum, K. M., Heien, M. L. A. V., Phillips, P. E. M., & Wightman, R. M.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2004-05-05
- Volume
- 24
- Issue
- 18
- Pages
- 4393-4400
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6729440
- OpenAlex
- W2164654255
- Cited by
- 343
- References
- 52
- Citations by year
- 2026: 9 · 2025: 11 · 2024: 10 · 2023: 6 · 2022: 12 · 2021: 16 · 2020: 19 · 2019: 15 · 2018: 8 · 2017: 21 · 2016: 16 · 2015: 17 · 2014: 17 · 2013: 14 · 2012: 30
- FWCI
- 11.70
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Funders
- National Institute on Drug Abuse (DA10900, R01DA010900)
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- cannabinoids, dopamine release, nucleus accumbens, CB1 receptor, catalepsy, locomotion, mesocorticolimbic dopamine system, ventral tegmental area, drug reinforcement
- MeSH terms
- Rimonabant, Animals, Cannabinoids, Dopamine, Dose-Response Relationship, Drug, Electric Stimulation, Electrochemistry, Electrodes, Implanted, Male, Medial Forebrain Bundle, Morpholines, Motor Activity, Naphthalenes, Synaptic Transmission, Nucleus Accumbens, Piperidines, Pyrazoles, Time Factors, Wakefulness, Rats, Sprague-Dawley, Receptor, Cannabinoid, CB1, Benzoxazines, Rats
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