Cannabinoid type 2 receptors in dopamine neurons inhibits psychomotor behaviors, alters anxiety, depression and alcohol preference
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Cannabinoid CB2 receptors (CB2Rs) are expressed in mouse brain dopamine (DA) neurons and are involved in several DA-related disorders. However, the cell type-specific mechanisms are unclear since the CB2R gene knockout mice are constitutive gene knockout. Therefore, we generated Cnr2-floxed mice that were crossed with DAT-Cre mice, in which Cre- recombinase expression is under dopamine transporter gene (DAT) promoter control to ablate Cnr2 gene in midbrain DA neurons of DAT-Cnr2 conditional knockout (cKO) mice. Using a novel sensitive RNAscope in situ hybridization, we detected CB2R mRNA expression in VTA DA neurons in wildtype and DAT-Cnr2 cKO heterozygous but not in the homozygous DAT-Cnr2 cKO mice. Here we report that the deletion of CB2Rs in dopamine neurons enhances motor activities, modulates anxiety and depression-like behaviors and reduces the rewarding properties of alcohol. Our data reveals that CB2Rs are involved in the tetrad assay induced by cannabinoids which had been associated with CB1R agonism. GWAS studies indicates that the CNR2 gene is associated with Parkinson’s disease and substance use disorders. These results suggest that CB2Rs in dopaminergic neurons may play important roles in the modulation of psychomotor behaviors, anxiety, depression, and pain sensation and in the rewarding effects of alcohol and cocaine.
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CB2 knockout in dopaminergic cells enhances forced-swim and tail-suspension immobility.
“CB2 knockout in dopaminergic cells enhances forced-swim and tail-suspension immobility [43].”
From The molecular and cellular mechanisms of depression: a focus on reward circuitry (2019) · cites this paper as [43]
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- [60]Onaivi ES Pharmacological characterization of cannabinoids in the elevated plus maze The J Pharmacol Exp Ther 1990 252 1002 1009 2162942
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- Authors
- Liu, Q.-R., Canseco-Alba, A., Zhang, H.-Y., Tagliaferro, P., Chung, M., Dennis, E., Sanabria, B., Schanz, N., Escosteguy-Neto, J. C., Ishiguro, H., Lin, Z., Sgro, S., Leonard, C. M., Santos-Junior, J. G., Gardner, E. L., Egan, J. M., Lee, J. W., Xi, Z.-X., & Onaivi, E. S.
- Affiliations
- William Paterson University (US)
- National Institute on Drug Abuse (US)
- University of Yamanashi (JP)
- Harvard University (US)
- Faculdade de Ciências Médicas da Santa Casa de São Paulo (BR)
- National Institutes of Health (US)
- Corresponding author
- Liu, Qing-Rong
- Onaivi, Emmanuel S.
- ORCID
- Venue
- Scientific Reports
- Published
- 2017-12-12
- Volume
- 7
- Issue
- 1
- Pages
- 17410-17410
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC5727179
- OpenAlex
- W2774541884
- Cited by
- 147
- References
- 69
- Citations by year
- 2026: 5 · 2025: 13 · 2024: 8 · 2023: 14 · 2022: 26 · 2021: 24 · 2020: 26 · 2019: 18 · 2018: 13
- FWCI
- 11.01
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- William Paterson University of New Jersey
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
- Consejo Nacional de Ciencia y Tecnología (232728)
- National Institutes of Health
- Japan Society for the Promotion of Science (18023009, 20023006, 20390098)
- National Institute on Aging
- National Institute on Drug Abuse (R01DA021409, DA021409, DA032890, R15DA032890)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R25HD082842)
- 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, CNR2, dopaminergic neurons, dopaminergic midbrain, conditional knockout mice, ventral tegmental area, psychomotor behavior, anxiety-like behavior, depression-like behavior, alcohol reward, Parkinson's disease, substance use disorders, pain sensation, cocaine reward
- MeSH terms
- Alcohol Drinking, Animals, Anxiety, Behavior, Animal, Choice Behavior, Depression, Mesencephalon, Mice, Transgenic, Motor Activity, Psychomotor Performance, Reward, RNA, Messenger, Tyrosine 3-Monooxygenase, Cocaine-Related Disorders, Receptor, Cannabinoid, CB2, Nociceptive Pain, Dopaminergic Neurons, Anhedonia
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