Morphine side effects in beta-arrestin 2 knockout mice.

Published

Journal Article

Morphine is a potent analgesic, yet, like most opioid narcotics, it exerts unwanted side effects such as constipation and respiratory suppression, thereby limiting its clinical utility. Pharmacological approaches taken to preserve the analgesic properties, while eliminating the unwanted side effects, have met with very limited success. Here, we provide evidence that altering mu opioid receptor regulation may provide a novel approach to discriminate morphine's beneficial and deleterious effects in vivo. We have previously reported that mice lacking the G protein-coupled receptor regulatory protein, beta-arrestin 2, display profoundly altered morphine responses. beta-Arrestin 2 knockout mice have enhanced and prolonged morphine analgesia with very little morphine tolerance. In this report, we examine whether the side effects of morphine treatment are also augmented in this animal model. Surprisingly, the genetic disruption of opioid receptor regulation, while enhancing and prolonging analgesia, dramatically attenuates the respiratory suppression and acute constipation caused by morphine.

Full Text

Duke Authors

Cited Authors

  • Raehal, KM; Walker, JKL; Bohn, LM

Published Date

  • September 2005

Published In

Volume / Issue

  • 314 / 3

Start / End Page

  • 1195 - 1201

PubMed ID

  • 15917400

Pubmed Central ID

  • 15917400

Electronic International Standard Serial Number (EISSN)

  • 1521-0103

International Standard Serial Number (ISSN)

  • 0022-3565

Digital Object Identifier (DOI)

  • 10.1124/jpet.105.087254

Language

  • eng