Cited by 160Cannabis and Cannabinoid ResearchTreatment of Major DepressionNeurotransmitter Receptor Influence on Behavior

Depression-like phenotype following chronic CB1 receptor antagonism

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Beyer, Chad E., Dwyer, Jason M., Piesla, Michael J., Platt, Brian J., Shen, Ru, Rahman, Zia, Chan, Karen, Manners, Melissa T. +4 more·2010·Neurobiology of Disease

Abstract

Rimonabant was the first clinically marketed cannabinoid (CB)(1) receptor antagonist developed to treat obesity. Unfortunately, CB(1) receptor antagonism produced adverse psychiatric events in patients. To determine whether this occurs pre-clinically, we investigated the effects of rimonabant in rodent models of mood disorders. Chronic treatment with rimonabant increased immobility time in the rat forced swim test and reduced the consumption of sucrose-sweetened water in an assay postulated to model anhedonia. These responses were similar to the effects elicited by chronic mild stress in these behavioral models, which, taken together, are indicative of a depression-like phenotype. Additionally, chronic treatment with rimonabant produced decreases in frontal cortex serotonin levels, marked reductions in hippocampal cell proliferation, survival, and BDNF levels, and elevations in the concentrations of pro-inflammatory cytokines including interferon gamma and TNF alpha. These preclinical findings mimic clinical reports and implicate possible mechanisms responsible for the unfavorable psychiatric events reported following chronic rimonabant use.

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Crossref · 10.1016/j.nbd.2010.03.020

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Authors
Beyer, C. E., Dwyer, J. M., Piesla, M. J., Platt, B. J., Shen, R., Rahman, Z., Chan, K., Manners, M. T., Samad, T. A., Kennedy, J. D., Bingham, B., & Whiteside, G. T.
Affiliations
Pfizer (United States) (US)
Corresponding author
Beyer, Chad E.
Venue
Neurobiology of Disease
Publisher
Elsevier BV
Published
2010-08
Volume
39
Issue
2
Pages
148-155
ISSN
0969-9961 (ISSN-L)
OpenAlex
W1970437559
Cited by
160
References
44
Citations by year
2026: 7 · 2025: 10 · 2024: 3 · 2023: 9 · 2022: 9 · 2021: 12 · 2020: 13 · 2019: 10 · 2018: 5 · 2017: 11 · 2016: 6 · 2015: 7 · 2014: 18 · 2013: 9 · 2012: 13
FWCI
9.23
Type
journal article
Language
en
Open access
Locations
  • Neurobiology of Disease (publishedVersion)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords
rimonabant, CB1 receptor antagonism, depression-like behavior, anhedonia, forced swim test, sucrose intake, chronic mild stress, serotonin, hippocampal neurogenesis, brain-derived neurotrophic factor, inflammatory cytokines, interferon-gamma, TNF-α, mood disorders
MeSH terms
Rimonabant, Analysis of Variance, Animals, Cell Survival, Disease Models, Animal, Flow Cytometry, Food Preferences, Frontal Lobe, Male, Phenotype, Piperidines, Pyrazoles, Stress, Psychological, Sucrose, Sweetening Agents, Swimming, Cytokines, Rats, Sprague-Dawley, Microdialysis, Brain-Derived Neurotrophic Factor, Receptor, Cannabinoid, CB1, Immobility Response, Tonic, Cell Proliferation, Rats

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