Antidepressant-like Effects of Buprenorphine are Mediated by Kappa Opioid Receptors
Open accessAbstract
Previous studies have identified potential antidepressant effects of buprenorphine (BPN), a drug with high affinity for mu opioid receptor (MORs) and kappa opioid receptors (KORs) and some affinity at delta opioid receptor (DOR) and opioid receptor-like 1 (ORL-1) receptors. Therefore, these studies examined which opioid receptors were involved in BPN's effects on animal behavior tests sensitive to antidepressant drugs. The acute effects of BPN were tested in the forced swim test (FST) using mice with genetic deletion of individual opioid receptors or after pharmacological blockade of receptors. For evaluating the effects of BPN on chronic stress, separate groups of mice were exposed to unpredictable chronic mild stress (UCMS) for 3 weeks and treated with BPN for at least 7 days before behavioral assessment and subsequent measurement of Oprk1, Oprm1, and Pdyn mRNA expression in multiple brain regions. BPN did not reduce immobility in mice with KOR deletion or after pretreatment with norbinaltorphimine, even though desipramine remained effective. In contrast, BPN reduced immobility in MOR and DOR knockout mice and in mice pretreated with the ORL-1 antagonist JTC-801. UCMS reduced sucrose preference, decreased time in the light side of the light/dark box, increased immobility in the FST and induced region-specific alterations in Oprk1, Oprm1, and PDYN mRNA expression in the frontal cortex and striatum. All of these changes were normalized following BPN treatment. The KOR was identified as a key player mediating the effects of BPN in tests sensitive to antidepressant drugs in mice. These studies support further development of BPN as a novel antidepressant.
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Buprenorphine, a partial μ-opioid receptor agonist and potent κ-opioid receptor antagonist, rescues the increase in immobility in the forced swim test produced by an unpredictable chronic mild stress model of depression in mice.
“buprenorphine, which is a partial μ-opioid receptor agonist and potent κ-opioid receptor antagonist rescues the increase in immobility in the forced swim test produced by an unpredictable chronic mild stress model of depression in mice (Falcon et al., 2016).”
From Mechanisms of ketamine and its metabolites as antidepressants (2022) · cites this paper as Falcon et al., 2016
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- Authors
- Falcon, E., Browne, C. A., Leon, R. M., Fleites, V. C., Sweeney, R., Kirby, L. G., & Lucki, I.
- Affiliations
- University of Pennsylvania (US)
- Temple University (US)
- Corresponding author
- Lucki, Irwin
- Venue
- Neuropsychopharmacology
- Published
- 2016-03-16
- Volume
- 41
- Issue
- 9
- Pages
- 2344-2351
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC4946065
- OpenAlex
- W2306924576
- Cited by
- 118
- References
- 34
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 4 · 2023: 11 · 2022: 13 · 2021: 12 · 2020: 22 · 2019: 15 · 2018: 18 · 2017: 8 · 2016: 2
- FWCI
- 8.06
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Pennsylvania
- U.S. Public Health Service (T32 MH14654, R01 MH92412)
- National Institute of Mental Health (R01MH092412, T32MH014654)
- National Institute on Drug Abuse (P30DA013429)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- buprenorphine, kappa opioid receptor, antidepressant effects, mu-opioid receptor, delta opioid receptor, opioid receptor-like 1, chronic unpredictable mild stress, forced swim test, OPRM1, prodynorphin, nor-binaltorphimine
- MeSH terms
- Animals, Antidepressive Agents, Behavior, Animal, Brain, Buprenorphine, Male, Mice, Inbred C57BL, Stress, Psychological, Receptors, Opioid, mu, Receptors, Opioid, delta, Receptors, Opioid, kappa, Mice, Knockout
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