Disruption of the κ‐opioid receptor gene in mice enhances sensitivity to chemical visceral pain, impairs pharmacological actions of the selective κ‐agonist U‐50,488H and attenuates morphine withdrawal
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***micro***-, delta- and kappa-opioid receptors are widely expressed in the central nervous system where they mediate the strong analgesic and mood-altering actions of opioids, and modulate numerous endogenous functions. To investigate the contribution of the kappa-opioid receptor (KOR) to opioid function in vivo, we have generated KOR-deficient mice by gene targeting. We show that absence of KOR does not modify expression of the other components of the opioid system, and behavioural tests indicate that spontaneous activity is not altered in mutant mice. The analysis of responses to various nociceptive stimuli suggests that the KOR gene product is implicated in the perception of visceral chemical pain. We further demonstrate that KOR is critical to mediate the hypolocomotor, analgesic and aversive actions of the prototypic kappa-agonist U-50, 488H. Finally, our results indicate that this receptor does not contribute to morphine analgesia and reward, but participates in the expression of morphine abstinence. Together, our data demonstrate that the KOR-encoded receptor plays a modulatory role in specific aspects of opioid function.
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During withdrawal, this up-regulation and subsequent activation of KOR may contribute to negative affect and thus promote relapse.
“During withdrawal, this up-regulation and subsequent activation of KOR may contribute to negative affect and thus promote relapse (Przewlocka et al 1997; Simonin et al 1998; Walker and Koob 2008).”
From The behavioral, anatomical and pharmacological parallels between social attachment, love and addiction (2012) · cites this paper as Simonin et al 1998
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- Authors
- Simonin, F., Valverde, O., Smadja, C., Slowe, S., Kitchen, I., Dierich, A., Le Meur, M., Roques, B. P., Maldonado, R., & Kieffer, B. L.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- University of Surrey (GB)
- Institut de génétique et de biologie moléculaire et cellulaire (FR)
- Corresponding author
- Kieffer, Brigitte L.
- Venue
- The EMBO Journal
- Published
- 1998-02-15
- Volume
- 17
- Issue
- 4
- Pages
- 886-897
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC1170438
- OpenAlex
- W2165005697
- Cited by
- 418
- References
- 65
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 5 · 2023: 13 · 2022: 5 · 2021: 11 · 2020: 11 · 2019: 6 · 2018: 18 · 2017: 11 · 2016: 14 · 2015: 17 · 2014: 23 · 2013: 18 · 2012: 17
- FWCI
- 8.37
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The EMBO Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Pfizer
- Association pour la Recherche sur le Cancer
- Institut National de la Santé et de la Recherche Médicale
- Ministère de l'Enseignement Supérieur et de la Recherche
- Ministère de l'Education Nationale, de l'Enseignement Supérieur et de la Recherche
- Centre National de la Recherche Scientifique
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pharmacological Receptor Mechanisms and Effects
- Keywords
- kappa opioid receptor, gene targeting, nociception, U50,488H, morphine withdrawal, morphine analgesia, opioid reward, opioid system, aversive effects, locomotor activity
- MeSH terms
- Animals, Behavior, Animal, Enkephalins, Female, Gene Expression Regulation, Male, Mice, Inbred C57BL, Morphine, Pain, Pro-Opiomelanocortin, Protein Precursors, Substance Withdrawal Syndrome, Viscera, Receptors, Opioid, kappa, Mice, Knockout, 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer, Mice
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