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Enhanced rewarding properties of morphine, but not cocaine, in beta arrestin-2 knock-out mice

Academic Article
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Overview

authors

  • Bohn, Laura
  • Gainetdinov, R. R.
  • Sotnikova, T. D.
  • Medvedev, I. O.
  • Lefkowitz, R. J.
  • Dykstra, L. A.
  • Caron, M. G.

publication date

  • November 2003

journal

  • Journal of Neuroscience  Journal

abstract

  • The reinforcing and psychomotor effects of morphine involve opiate stimulation of the dopaminergic system via activation of mu-opioid receptors (muOR). Both mu-opioid and dopamine receptors are members of the G-protein-coupled receptor (GPCR) family of proteins. GPCRs are known to undergo desensitization involving phosphorylation of the receptor and the subsequent binding of beta(arrestins), which prevents further receptor-G-protein coupling. Mice lacking beta(arrestin)-2 (beta(arr2)) display enhanced sensitivity to morphine in tests of pain perception attributable to impaired desensitization of muOR. However, whether abrogating muOR desensitization affects the reinforcing and psychomotor properties of morphine has remained unexplored. In the present study, we examined this question by assessing the effects of morphine and cocaine on locomotor activity, behavioral sensitization, conditioned place preference, and striatal dopamine release in beta(arr2) knock-out (beta(arr2)-KO) mice and their wild-type (WT) controls. Cocaine treatment resulted in very similar neurochemical and behavioral responses between the genotypes. However, in the beta(arr2)-KO mice, morphine induced more pronounced increases in striatal extracellular dopamine than in WT mice. Moreover, the rewarding properties of morphine in the conditioned place preference test were greater in the beta(arr2)-KO mice when compared with the WT mice. Thus, beta(arr2) appears to play a more important role in the dopaminergic effects mediated by morphine than those induced by cocaine.

subject areas

  • Animals
  • Arrestins
  • Behavior, Animal
  • Cocaine
  • Corpus Striatum
  • Dopamine
  • Male
  • Mice
  • Mice, Knockout
  • Microdialysis
  • Morphine
  • Motor Activity
  • Reward
  • Spatial Behavior
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Research

keywords

  • beta arrestin
  • cocaine
  • conditioned place preference
  • dopamine
  • knock
  • locomotor activity
  • microdialysis
  • morphine
  • out mice
  • sensitization
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Identity

International Standard Serial Number (ISSN)

  • 0270-6474

PubMed ID

  • 14614085
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Additional Document Info

start page

  • 10265

end page

  • 10273

volume

  • 23

issue

  • 32

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