Differential effects of the antidepressants tranylcypromine and fluoxetine on limbic cannabinoid receptor binding and endocannabinoid contents
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The goal of this study was to determine whether the endocannabinoid system is altered by chronic antidepressant treatment. The effects of 3-week administration of the monoamine oxidase inhibitor, tranylcypromine (10 mg/kg) and the selective serotonin reuptake inhibitor, fluoxetine (5 mg/kg) on cannabinoid CB(1) receptor densities and endocannabinoid contents were determined in limbic brain regions of the rat. Tranylcypromine significantly reduced tissue content of the endocannabinoid N-arachidonylethanolamine (anandamide) in the prefrontal cortex, hippocampus and hypothalamus and increased 2-arachidonoylglycerol content in the prefrontal cortex. Tranylcypromine treatment significantly increased CB(1) receptor binding density in the prefrontal cortex and hippocampus, but not in the hypothalamus. Treatment with fluoxetine increased CB(1) receptor density in the prefrontal cortex, but had no effect on endocannabinoid contents in any brain region examined. These data suggest that monoaminergic neurotransmission can regulate the endocannabinoid system and further indicates a role of the endocannabinoid system in affective illness and its treatment.
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2-AG levels are reduced in individuals with major depression.
“two independent studies have now both reported that 2-AG levels are reduced in individuals with major depression (Hill et al., 2008; Hill et al., 2009)”
From The endocannabinoid system as a target for novel anxiolytic drugs (2017) · cites this paper as Hill et al., 2008
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The endocannabinoid system as a target for novel anxiolytic drugs
Patel, S., Hill, M. N., Cheer, J. F., Wotjak, C. T., & Holmes, A. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.12.033 · Cited by 233 · see citing works
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Sciolino, N. R., Bortolato, M., Eisenstein, S. A., Fu, J., Oveisi, F., Hohmann, A. G., & Piomelli, D. (2010) · Neuroscience · doi:10.1016/j.neuroscience.2010.04.007 · Cited by 89 · see citing works
- Authors
- Hill, M. N., Ho, W.-S. V., 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 Neural Transmission
- Published
- 2008-10-31
- Volume
- 115
- Issue
- 12
- Pages
- 1673-1679
- ISSN
- 0300-9564 (ISSN-L)
- 1435-1463
- PMC
- PMC2992975
- OpenAlex
- W1980665999
- Cited by
- 75
- References
- 41
- Citations by year
- 2026: 6 · 2025: 3 · 2024: 2 · 2023: 3 · 2022: 4 · 2021: 9 · 2020: 5 · 2019: 4 · 2018: 4 · 2017: 5 · 2016: 1 · 2015: 5 · 2014: 8 · 2013: 4 · 2012: 2
- FWCI
- 2.34
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Journal of Neural Transmission (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Drug Abuse (R21DA022439)
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- tranylcypromine, fluoxetine, endocannabinoid system, anandamide, 2-arachidonoylglycerol, monoamine oxidase inhibitors, selective serotonin reuptake inhibitors, limbic system, prefrontal cortex, hippocampus, hypothalamus, chronic antidepressant treatment, monoaminergic neurotransmission, affective illness
- MeSH terms
- Animals, Antidepressive Agents, Arachidonic Acids, Binding, Competitive, Brain, Depressive Disorder, Fluoxetine, Glycerides, Ligands, Limbic System, Male, Monoamine Oxidase Inhibitors, Synaptic Transmission, Tranylcypromine, Biogenic Monoamines, Up-Regulation, Rats, Sprague-Dawley, Selective Serotonin Reuptake Inhibitors, Receptor, Cannabinoid, CB1, Rats, Polyunsaturated Alkamides, Cannabinoid Receptor Modulators, Endocannabinoids
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