Journal
INTERNATIONAL JOURNAL OF NEUROSCIENCE
Volume 125, Issue 1, Pages 56-65Publisher
TAYLOR & FRANCIS LTD
DOI: 10.3109/00207454.2014.896913
Keywords
morphine; analgesia; tolerance; beta-arrestin; gene silencing
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Funding
- National Natural Science Foundation of China [81171259, 30700783]
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beta-arrestin 2, a regulatory molecule of G protein-coupled receptor, has been proved to play an important role in regulating functions of mu opioid receptor. Changes of beta-arrestin 2 expression might affect the function of mu opioid receptors and the effect of its agonists. In this study, antigene RNAs (agRNAs), which could selectively target gene transcription start sites and potently inhibit gene expression, were used to downregulate the expression of beta-arrestin 2 to investigate its effects on morphine analgesia and tolerance in mice. After intracerebroventricular administration of recombinant lentivirus encoding beta-arrestin 2 agRNAs to the mice, beta-arrestin 2 expression was significantly decreased for more than 3 weeks. Mice treated with beta-arrestin 2 agRNAs showed enhanced analgesic effects in response to morphine and failed to develop antinociceptive tolerance. These results suggest that inhibition of beta-arrestin 2 in the brain with specific agRNAs can improve morphine efficacy, and consequently provide us a useful strategy for treatment of chronic intractable pain and morphine tolerance in vivo.
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