Cited by 401Cannabis and Cannabinoid ResearchNeurotransmitter Receptor Influence on BehaviorNeuroscience and Neuropharmacology Research

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Brain cannabinoid CB2 receptors modulate cocaine's actions in mice

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Xi, Zheng-Xiong, Peng, Xiao-Qing, Li, Xia, Song, Rui, Zhang, Hai-Ying, Liu, Qing-Rong, Yang, Hong-Ju, Bi, Guo-Hua, Li, Jie, Gardner, Eliot L·2011·Nature Neuroscience

DOI 10.1038/nn.2874PMC PMC3164946

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Abstract

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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Self-citation
BindingDB Entry 50005370: Design, synthesis, and biological evaluation of aminoalkylindole derivatives as cannabinoid receptor ligands with potential for treatment of alcohol abuse.
BindingDB (2020) · UC San Diego · doi:10.7270/q25m68m1
BindingDB Entry 50042536: Novel triaryl sulfonamide derivatives as selective cannabinoid receptor 2 inverse agonists and osteoclast inhibitors: discovery, optimization, and biological evaluation.
BindingDB (2013) · UC San Diego · doi:10.7270/q2bk1dpw
BindingDB Entry 50040733: Lead discovery, chemistry optimization, and biological evaluation studies of novel biamide derivatives as CB2 receptor inverse agonists and osteoclast inhibitors.
BindingDB (2013) · UC San Diego · doi:10.7270/q22808r5
BindingDB Entry 50042588: TBA
BindingDB (2013) · UC San Diego · doi:10.7270/q2mp54mq

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: Xi, Zheng-Xiong
Peng, Xiao-Qing
Li, Xia
Song, Rui
Zhang, Hai-Ying
Liu, Qing-Rong
Bi, Guo-Hua
Li, Jie
Gardner, Eliot L
Venue: Nature Neuroscience
Publisher: Springer Science and Business Media LLC
Published: 2011-07-24
Volume: 14
Issue: 9
Pages: 1160-1166
ISSN: 1097-6256 (ISSN-L)
1546-1726
DOI: 10.1038/nn.2874
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 (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: 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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