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

Bohn, Laura M

Gainetdinov, Raul R

Sotnikova, Tatyana D

Medvedev, Ivan O

Lefkowitz, Robert J

Dykstra, Linda A

Caron, Marc G

United States

2012-10-24T20:17:06Z

2003-11-12

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.

http://www.ncbi.nlm.nih.gov/pubmed/14614085

23/32/10265

1529-2401

https://hdl.handle.net/10161/5935

eng

Society for Neuroscience

J Neurosci

Journal of Neuroscience

Animals

Arrestins

Behavior, Animal

Cocaine

Corpus Striatum

Dopamine

Male

Mice

Mice, Knockout

Microdialysis

Morphine

Motor Activity

Reward

Spatial Behavior

beta-Arrestin 2

beta-Arrestins

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

Journal article

Lefkowitz, Robert J|0000-0003-1472-7545

32

23

http://www.ncbi.nlm.nih.gov/pubmed/14614085

10265

10273

32

Basic Science Departments

Biochemistry

Cell Biology

Chemistry

Clinical Science Departments

Duke

Duke Cancer Institute

Duke Institute for Brain Sciences

Institutes and Centers

Institutes and Provost's Academic Units

Medicine

Medicine, Cardiology

Neurobiology

Pathology

School of Medicine

Trinity College of Arts & Sciences

University Institutes and Centers

Published

23