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Two Brain Sites for Cannabinoid Reward
Open accessAbstract
The recent findings that Delta9tetrahydrocannabinol (Delta9THC), the active agent in marijuana and hashish, (1) is self-administered intravenously, (2) potentiates the rewarding effects of electrical brain stimulation, and (3) can establish conditioned place preferences in laboratory animals, suggest that these drugs activate biologically primitive brain reward mechanisms. Here, we identify two chemical trigger zones for stimulant and rewarding actions of Delta9THC. Microinjections of Delta9THC into the posterior ventral tegmental area (VTA) or into the shell of the nucleus accumbens (NAS) increased locomotion, and rats learned to lever-press for injections of Delta9THC into each of these regions. Substitution of vehicle for drug or treatment with a cannabinoid CB1 receptor antagonist caused response cessation. Microinjections of Delta9THC into the posterior VTA and into the posterior shell of NAS established conditioned place preferences. Injections into the core of the NAS, the anterior VTA, or dorsal to the VTA were ineffective. These findings link the sites of rewarding action of Delta9THC to brain regions where such drugs as amphetamines, cocaine, heroin, and nicotine are also thought to have their sites of rewarding action.
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“Similarly, rats and mice learn to self-administer opiates (Bozarth and Wise, 1981; Welzl et al., 1989; David and Cazala, 1994a; 1994b; Devine and Wise, 1994), cannabinoids (Zangen et al., 2006), cocaine (David et al., 2004; Rodd et al., 2005) or ethanol (Gatto et al., 1994; Rodd-Henricks et al., 2000) into the VTA.”
From Dopamine reward circuitry: Two projection systems from the ventral midbrain to the nucleus accumbens–olfactory tubercle complex (2007) · cites this paper as Zangen et al., 2006
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“The VTA at least partly mediates the rewarding effects of nicotine, opiates, cannabinoids and ethanol.”
From Dopamine reward circuitry: Two projection systems from the ventral midbrain to the nucleus accumbens–olfactory tubercle complex (2007) · cites this paper as Zangen et al., 2006
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Metadata
- Authors
- Zangen, A., Solinas, M., Ikemoto, S., Goldberg, S. R., & Wise, R. A.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Wise, Roy A.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2006-05-03
- Volume
- 26
- Issue
- 18
- Pages
- 4901-4907
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6674153
- OpenAlex
- W1994818402
- Cited by
- 174
- References
- 42
- Citations by year
- 2026: 2 · 2025: 3 · 2023: 4 · 2022: 7 · 2021: 4 · 2020: 6 · 2019: 5 · 2018: 9 · 2017: 11 · 2016: 5 · 2015: 11 · 2014: 10 · 2013: 13 · 2012: 5
- FWCI
- 9.88
- 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)
- 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
- delta-9-tetrahydrocannabinol, ventral tegmental area, nucleus accumbens shell, conditioned place preference, locomotor activity, self-administration, CB1 receptor antagonist
- MeSH terms
- Analysis of Variance, Animals, Behavior, Animal, Cannabinoids, Conditioning, Operant, Male, Motor Activity, Nucleus Accumbens, Psychotropic Drugs, Reward, Self Stimulation, Dronabinol, Time Factors, Rats, Sprague-Dawley, Ventral Tegmental Area, Rats
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