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Marijuana and cannabinoid regulation of brain reward circuits
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The reward circuitry of the brain consists of neurons that synaptically connect a wide variety of nuclei. Of these brain regions, the ventral tegmental area (VTA) and the nucleus accumbens (NAc) play central roles in the processing of rewarding environmental stimuli and in drug addiction. The psychoactive properties of marijuana are mediated by the active constituent, Delta(9)-THC, interacting primarily with CB1 cannabinoid receptors in a large number of brain areas. However, it is the activation of these receptors located within the central brain reward circuits that is thought to play an important role in sustaining the self-administration of marijuana in humans, and in mediating the anxiolytic and pleasurable effects of the drug. Here we describe the cellular circuitry of the VTA and the NAc, define the sites within these areas at which cannabinoids alter synaptic processes, and discuss the relevance of these actions to the regulation of reinforcement and reward. In addition, we compare the effects of Delta(9)-THC with those of other commonly abused drugs on these reward circuits, and we discuss the roles that endogenous cannabinoids may play within these brain pathways, and their possible involvement in regulating ongoing brain function, independently of marijuana consumption. We conclude that, whereas Delta(9)-THC alters the activity of these central reward pathways in a manner that is consistent with other abused drugs, the cellular mechanism through which this occurs is likely different, relying upon the combined regulation of several afferent pathways to the VTA.
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“The actions of cannabinoids in the VTA may be more complex than those of opiates, but appear to involve disinhibitory mechanisms to activate dopamine neurons (Lupica et al., 2004; Gardner, 2005).”
From Dopamine reward circuitry: Two projection systems from the ventral midbrain to the nucleus accumbens–olfactory tubercle complex (2007) · cites this paper as Lupica et al., 2004
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Metadata
- Authors
- Lupica, C. R., Riegel, A. C., & Hoffman, A. F.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Lupica, Carl R
- Venue
- British Journal of Pharmacology
- Publisher
- Wiley
- Published
- 2004-09
- Volume
- 143
- Issue
- 2
- Pages
- 227-234
- ISSN
- 0007-1188 (ISSN-L)
- 1476-5381
- PMC
- PMC1575338
- OpenAlex
- W1993599253
- Cited by
- 289
- References
- 85
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 10 · 2023: 10 · 2022: 17 · 2021: 15 · 2020: 16 · 2019: 12 · 2018: 13 · 2017: 14 · 2016: 12 · 2015: 17 · 2014: 13 · 2013: 6 · 2012: 13
- FWCI
- 1.64
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- British Journal of Pharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › 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
- cannabis, delta-9-tetrahydrocannabinol, CB1 receptor, brain reward circuits, ventral tegmental area, nucleus accumbens, drug addiction, self-administration, synaptic regulation, endocannabinoids, reinforcement, psychoactive effects
- MeSH terms
- Animals, Brain, Cannabinoids, Humans, National Institutes of Health (U.S.), Reward, United States
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