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Regional alterations in the endocannabinoid system in an animal model of depression: effects of concurrent antidepressant treatment
Open accessAbstract
It has been suggested that disturbances in endocannabinoid signaling contribute to the development of depressive illness; however, at present there is insufficient evidence to allow for a full understanding of this role. To further this understanding, we performed an analysis of the endocannabinoid system in an animal model of depression. Male rats exposed to chronic, unpredictable stress (CUS) for 21 days exhibited a reduction in sexual motivation, consistent with the hypothesis that CUS in rats induces depression‐like symptoms. We determined the effects of CUS, with or without concurrent treatment with the antidepressant imipramine (10 mg/kg), on CP55940 binding to the cannabinoid CB 1 receptor; whole tissue endocannabinoid content; and fatty acid amide hydrolase (FAAH) activity in the prefrontal cortex, hippocampus, hypothalamus, amygdala, midbrain and ventral striatum. Exposure to CUS resulted in a significant increase in CB 1 receptor binding site density in the prefrontal cortex and a decrease in CB 1 receptor binding site density in the hippocampus, hypothalamus and ventral striatum. Except in the hippocampus, these CUS‐induced alterations in CB 1 receptor binding site density were attenuated by concurrent antidepressant treatment. CUS alone produced a significant reduction in N‐arachidonylethanolamine (anandamide) content in every brain region examined, which was not reversed by antidepressant treatment. These data suggest that the endocannabinoid system in cortical and subcortical structures is differentially altered in an animal model of depression and that the effects of CUS on CB 1 receptor binding site density are attenuated by antidepressant treatment while those on endocannabinoid content are not.
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“Animal studies17 have shown that chronic stress is associated with decreased brain levels of the endocannabinoid anandamide and CB1 receptor adaptations17–19”
From Elevated brain cannabinoid CB1 receptor availability in post-traumatic stress disorder: A positron emission tomography study (2013) · cites this paper as [19]
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Metadata
- Authors
- Hill, M. N., Carrier, E. J., McLaughlin, R. J., Morrish, A. C., Meier, S. E., Hillard, C. J., & Gorzalka, B. B.
- Affiliations
- University of British Columbia (CA)
- Medical College of Wisconsin (US)
- Corresponding author
- Gorzalka, Boris B.
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2008-09
- Volume
- 106
- Issue
- 6
- Pages
- 2322-2336
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- PMC
- PMC2606621
- OpenAlex
- W2009594014
- Cited by
- 246
- References
- 98
- Citations by year
- 2026: 7 · 2025: 11 · 2024: 11 · 2023: 11 · 2022: 15 · 2021: 22 · 2020: 16 · 2019: 13 · 2018: 15 · 2017: 13 · 2016: 8 · 2015: 12 · 2014: 17 · 2013: 15 · 2012: 12
- FWCI
- 11.21
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Michael Smith Health Research BC
- National Institutes of Health
- Canadian Institutes of Health Research
- Natural Sciences and Engineering Research Council of Canada
- National Institute on Drug Abuse (DA 16967, R01DA016967)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Cannabis and Cannabinoid Research
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Keywords
- endocannabinoid system, depression, chronic unpredictable mild stress, imipramine, antidepressant treatment, fatty acid amide hydrolase, anandamide, regional brain differences, prefrontal cortex, hippocampus, hypothalamus, amygdala, ventral striatum, sexual motivation
- MeSH terms
- Analgesics, Animals, Antidepressive Agents, Antidepressive Agents, Tricyclic, Arachidonic Acids, Brain, Cyclohexanols, Major Depressive Disorder, Disease Models, Animal, Imipramine, Male, Motivation, Sexual Behavior, Animal, Stress, Psychological, Rats, Long-Evans, Receptor, Cannabinoid, CB1, Rats, Polyunsaturated Alkamides, Cannabinoid Receptor Modulators, Endocannabinoids
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