Premium
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
Author(s) -
Simonin Frédéric,
Valverde Olga,
Smadja Claire,
Slowe Susan,
Kitchen Ian,
Dierich Andrée,
Le Meur Marianne,
Roques Bernard P.,
Maldonado Rafael,
Kieffer Brigitte L.
Publication year - 1998
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/17.4.886
Subject(s) - κ opioid receptor , agonist , morphine , dynorphin , opioid , receptor , pharmacology , biology , kappa , neuroscience , analgesic , μ opioid receptor , opioid receptor , opioid peptide , biochemistry , linguistics , philosophy
μ‐, δ‐ and κ‐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 κ‐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 κ‐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.