Opioid receptors: Distinct roles in mood disorders
Open accessAbstract
The roles of opioid receptors in pain and addiction have been extensively studied, but their function in mood disorders has received less attention. Accumulating evidence from animal research reveals that mu, delta and kappa opioid receptors (MORs, DORs and KORs, respectively) exert highly distinct controls over mood-related processes. DOR agonists and KOR antagonists have promising antidepressant potential, whereas the risk-benefit ratio of currently available MOR agonists as antidepressants remains difficult to evaluate, in addition to their inherent abuse liability. To date, both human and animal studies have mainly examined MORs in the etiology of depressive disorders, and future studies will address DOR and KOR function in established and emerging neurobiological aspects of depression, including neurogenesis, neurodevelopment, and social behaviors.
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Opioids are recognized as the most powerful and effective drugs for relief of acute pain in humans and relieve pain and suffering, including negative emotional states.
“Opioids are recognized as the most powerful and effective drugs for the relief of acute pain in humans, and a unifying common theme is their relief of pain and suffering, including negative emotional states (Lutz and Kieffer, 2013).”
From Drug Addiction: Hyperkatifeia/Negative Reinforcement as a Framework for Medications Development (2021) · cites this paper as Lutz and Kieffer, 2013
The Introduction describes morphine as a highly potent, widely used painkiller and says opioid drugs have euphoric effects and influence mood. It does not establish that opioids are the most powerful and effective drugs specifically for acute pain in humans, or that opioids generally relieve negative emotional states; the paper describes distinct mood effects across opioid receptors. (LLM, conf=0.87)
Experimental — accuracy not yet measuredCell subtype enriched peptides such as dynorphin and enkephalin play a role in depression.
“Among the many neuropeptides found within the NAc, cell subtype enriched peptides such as dynorphin and enkephalin play a role in depression (71, 72).”
From Emerging Role for Nucleus Accumbens Medium Spiny Neuron Subtypes in Depression (2017) · cites this paper as [72]
The antidepressant activity of buprenorphine is in line with pharmacological studies where mu-opioid receptor agonism was correlated with increases in dopamine levels, enhancement of hedonic tone, and sense of contentment.
“Overall, these results regarding the potential antidepressant activity of BUP, are in line with existing pharmacological studies where the agonism of MORs was correlated with increases in dopamine levels, enhancement of hedonic tone and sense of contentment, which together are responsible of the antidepressant activity [29].”
From The Efficacy of Buprenorphine in Major Depression, Treatment-Resistant Depression and Suicidal Behavior: A Systematic Review (2018) · cites this paper as [29]
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- Authors
- Lutz, P.-E., & Kieffer, B. L.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Kieffer, Brigitte L.
- ORCID
- Kieffer, Brigitte L.
- Venue
- Trends in Neurosciences
- Publisher
- Elsevier BV
- Published
- 2013-03
- Volume
- 36
- Issue
- 3
- Pages
- 195-206
- ISSN
- 0166-2236 (ISSN-L)
- PMC
- PMC3594542
- OpenAlex
- W2071801806
- Cited by
- 542
- References
- 154
- Citations by year
- 2026: 32 · 2025: 45 · 2024: 28 · 2023: 32 · 2022: 32 · 2021: 40 · 2020: 72 · 2019: 59 · 2018: 56 · 2017: 38 · 2016: 33 · 2015: 30 · 2014: 34 · 2013: 11
- FWCI
- 2.56
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Trends in Neurosciences (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion, other-oa)
- Funders
- European Commission
- Institut National de la Santé et de la Recherche Médicale
- Fondation pour la Recherche Médicale
- Fondation Fyssen
- Université de Strasbourg (16658)
- Centre National de la Recherche Scientifique
- National Institutes of Health (05010)
- U.S. Public Health Service (05010, 16658)
- National Institute on Drug Abuse (P50DA005010)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- opioid receptors, mood disorders, depression, mu-opioid receptor, delta opioid receptor, kappa opioid receptor, antidepressant potential, opioid agonists, abuse liability, neurogenesis, brain development, social behavior
- MeSH terms
- Affect, Analgesics, Opioid, Animals, Antidepressive Agents, Brain Chemistry, Female, Humans, Male, Maternal Behavior, Models, Neurological, Narcotic Antagonists, Nerve Tissue Proteins, Neuronal Plasticity, Pregnancy, Prenatal Exposure Delayed Effects, Receptors, Opioid, Reward, Social Behavior, Comorbidity, Mice, Knockout, Neurotransmitter Agents, Opioid Peptides, Brain-Derived Neurotrophic Factor, Mood Disorders, Substance-Related Disorders, Mice, Neurogenesis
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