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- Title
Evidence for a role of CaMKIV in the development of opioid analgesic tolerance.
- Authors
Ko, Shanelle W.; Jia, Yongheng; Xu, Hui; Yim, Se‐Jeong; Jang, Dong‐Hyuk; Lee, Yong‐Seok; Zhao, Ming‐Gao; Toyoda, Hiroki; Wu, Long‐Jun; Chatila, Talal; Kaang, Bong‐Kiun; Zhuo, Min
- Abstract
cAMP response-element binding protein (CREB), a transcription factor involved in learning, memory and drug addiction, is phosphorylated by calcium–calmodulin-dependent protein kinase IV (CaMKIV). Here, we show that CaMKIV-knockout (KO) mice developed less analgesic tolerance after chronic morphine administration with no alteration in physical dependence or acute morphine-induced analgesia. The increase in phosphorylated CREB expression observed in wild-type mice after chronic morphine was absent in CaMKIV-KO mice, while there was no difference in the expression or phosphorylation of the µ-opioid receptor between groups. Morphine-treated CaMKIV-KO mice showed less G-protein uncoupling from the µ-opioid receptor than did wild-type mice, while uncoupling was similar in control wild-type and KO mice. In addition, morphine reduced inhibitory transmission to a greater degree in CaMKIV-KO mice than in controls after chronic morphine exposure. Our results provide novel evidence for the role of CaMKIV in the development of opioid analgesic tolerance but not physical dependence.
- Subjects
CYCLIC adenylic acid; CARRIER proteins; TRANSCRIPTION factors; PHOSPHORYLATION; G proteins
- Publication
European Journal of Neuroscience, 2006, Vol 23, Issue 8, p2158
- ISSN
0953-816X
- Publication type
Article
- DOI
10.1111/j.1460-9568.2006.04748.x