Dataset Information

Genetic dissociation of morphine analgesia from hyperalgesia in mice.

ABSTRACT:

Rationale

Morphine is the prototypic mu opioid, producing its analgesic actions through traditional 7 transmembrane domain (7TM) G-protein-coupled receptors generated by the mu opioid receptor gene (Oprm1). However, the Oprm1 gene undergoes extensive alternative splicing to yield three structurally distinct sets of splice variants. In addition to the full-length 7TM receptors, it produces a set of truncated variants comprised of only 6 transmembrane domains (6TM).

Objectives

This study explored the relative contributions of 7TM and 6TM variants in a range of morphine actions.

Methods

Groups of male and mixed-gender wild-type and exon 11 Oprm1 knockout mice were examined in a series of behavioral assays measuring analgesia, hyperalgesia, respiration, and reward in conditioned place preference assays.

Results

Loss of the 6TM variants in an exon 11 knockout (E11 KO) mouse did not affect morphine analgesia, reward, or respiratory depression. However, E11 KO mice lacking 6TM variants failed to show morphine-induced hyperalgesia, developed tolerance more slowly than wild-type mice, and did not display hyperlocomotion.

Conclusions

Together, our findings confirm the established role of 7TM mu receptor variants in morphine analgesia, reward, and respiratory depression, but reveal an unexpected obligatory role for 6TM variants in morphine-induced hyperalgesia and a modulatory role in morphine tolerance and dependence.

SUBMITTER: Marrone GF

PROVIDER: S-EPMC5520541 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Publications

Genetic dissociation of morphine analgesia from hyperalgesia in mice.

Marrone Gina F GF Le Rouzic Valerie V Varadi Andras A Xu Jin J Rajadhyaksha Anjali M AM Majumdar Susruta S Pan Ying-Xian YX Pasternak Gavril W GW

Psychopharmacology 20170325 12

<h4>Rationale</h4>Morphine is the prototypic mu opioid, producing its analgesic actions through traditional 7 transmembrane domain (7TM) G-protein-coupled receptors generated by the mu opioid receptor gene (Oprm1). However, the Oprm1 gene undergoes extensive alternative splicing to yield three structurally distinct sets of splice variants. In addition to the full-length 7TM receptors, it produces a set of truncated variants comprised of only 6 transmembrane domains (6TM).<h4>Objectives</h4>This ...[more]

PMID: 28343361

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Dataset Information

Genetic dissociation of morphine analgesia from hyperalgesia in mice.

Rationale

Objectives

Methods

Results

Conclusions

Publications

Genetic dissociation of morphine analgesia from hyperalgesia in mice.

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