Brain cannabinoid CB2 receptors modulate cocaine's actions in mice
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The presence and function of cannabinoid CB(2) receptors in the brain have been the subjects of much debate. We found that systemic, intranasal or intra-accumbens local administration of JWH133, a selective CB(2) receptor agonist, dose-dependently inhibited intravenous cocaine self-administration, cocaine-enhanced locomotion, and cocaine-enhanced accumbens extracellular dopamine in wild-type and CB(1) receptor knockout (CB(1)(-/-), also known as Cnr1(-/-)) mice, but not in CB(2)(-/-) (Cnr2(-/-)) mice. This inhibition was mimicked by GW405833, another CB(2) receptor agonist with a different chemical structure, and was blocked by AM630, a selective CB(2) receptor antagonist. Intra-accumbens administration of JWH133 alone dose-dependently decreased, whereas intra-accumbens administration of AM630 elevated, extracellular dopamine and locomotion in wild-type and CB(1)(-/-) mice, but not in CB(2)(-/-) mice. Intra-accumbens administration of AM630 also blocked the reduction in cocaine self-administration and extracellular dopamine produced by systemic administration of JWH133. These findings suggest that brain CB(2) receptors modulate cocaine's rewarding and locomotor-stimulating effects, likely by a dopamine-dependent mechanism.
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CB2R is mainly found in the periphery but also in some microglia and neuronal populations in the CNS.
“whereas CB2R is mainly found in the periphery but also in some microglia and neuronal populations in the central nervous system (CNS) [15,16]”
From Amygdala FAAH and anandamide: mediating protection and recovery from stress (2013) · cites this paper as [16]
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Self-citation
- Authors
- Xi, Z.-X., Peng, X.-Q., Li, X., Song, R., Zhang, H.-Y., Liu, Q.-R., Yang, H.-J., Bi, G.-H., Li, J., & Gardner, E. L.
- Affiliations
- National Institute on Drug Abuse (US)
- Corresponding author
- Xi, Zheng-Xiong
- ORCID
- Venue
- Nature Neuroscience
- Published
- 2011-07-24
- Volume
- 14
- Issue
- 9
- Pages
- 1160-1166
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC3164946
- OpenAlex
- W1989353122
- Cited by
- 397
- References
- 50
- Citations by year
- 2026: 9 · 2025: 13 · 2024: 14 · 2023: 16 · 2022: 30 · 2021: 34 · 2020: 23 · 2019: 27 · 2018: 25 · 2017: 31 · 2016: 30 · 2015: 27 · 2014: 37 · 2013: 35 · 2012: 37
- FWCI
- 28.11
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (Z99 DA999999)
- 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
- CB2 receptor, cocaine self-administration, nucleus accumbens, JWH-133, AM630, dopamine, drug reward, CB2 receptor agonist
- MeSH terms
- Administration, Intranasal, Analysis of Variance, Animals, Brain, Cannabinoids, Cocaine, Conditioning, Operant, Indoles, Male, Mice, Inbred C57BL, Motor Activity, Self Administration, Microdialysis, Mice, Knockout, Dopamine Uptake Inhibitors, Receptor, Cannabinoid, CB1, Receptor, Cannabinoid, CB2, Rotarod Performance Test, Mice
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