Improvement of morphine-mediated analgesia by inhibition of β-arrestin2 expression in mice periaqueductal gray matter.
Morphine is a well-known mu-opioid receptor (MOR) agonist and an efficient analgesic, but its long-term use inevitably leads to drug addiction and tolerance. Here, we show that specific inhibition of beta-arrestin2 with its siRNA lentivirus microinjected in mice periaqueductal gray matter (PAG) significantly improved both acute and chronic morphine analgesia and delayed the tolerance in the hotplate test. The specific effect of beta-arrestin2 was proven by overexpression or knockdown of its homology beta-arrestin1 in PAG, which showed no significant effects on morphine analgesia. These findings suggest that specific siRNA targeting beta-arrestin2 may constitute a new approach to morphine therapy and other MOR agonist-mediated analgesia and tolerance.
Li
Yuting
Y
Department of Pharmacology, Shenyang Pharmaceutical University, P R China. genggeng800816@yahoo.com
Liu
Xing
X
Liu
Chang
C
Kang
Jiuhong
J
Yang
Jingyu
J
Pei
Gang
G
Wu
Chunfu
C
D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D019390:Arrestins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D051379:Mice; D008845:Microinjections; D009020:Morphine / Q000008:administration & dosage* / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects; D010487:Periaqueductal Gray / Q000187:drug effects / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins
C000605254:ARRB2 protein, human; D000701:Analgesics, Opioid; C000605258:Arrb2 protein, mouse; D019390:Arrestins; D034741:RNA, Small Interfering; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins; D009020:Morphine