Cited by 75Cannabis and Cannabinoid ResearchTreatment of Major DepressionNeuroscience and Neuropharmacology Research

Differential effects of the antidepressants tranylcypromine and fluoxetine on limbic cannabinoid receptor binding and endocannabinoid contents

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Hill, Matthew N., Ho, Wing-Sze Vanessa, Hillard, Cecilia J., Gorzalka, Boris B.·2008·Journal of Neural Transmission

Abstract

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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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
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
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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